Skip to main content


  • Research
  • Open Access

The orosomucoid 1 protein (α1 acid glycoprotein) is overexpressed in odontogenic myxoma

  • 1,
  • 1Email author,
  • 2, 3,
  • 1,
  • 1,
  • 4,
  • 5,
  • 5 and
  • 6
Proteome Science201210:49

  • Received: 7 February 2012
  • Accepted: 3 August 2012
  • Published:



Odontogenic myxoma (OM) is a benign, but locally invasive, neoplasm occurring in the jaws. However, the molecules implicated in its development are unknown. OM as well as Dental Follicle (DF), an odontogenic tissue surrounding the enamel organ, is derived from ectomesenchymal/mesencyhmal elements. To identify some protein that could participate in the development of this neoplasm, total proteins from OM were separated by two-dimensional electrophoresis and the profiles were compared with those obtained from DF, used as a control.


We identified eight proteins with differential expression; two of them were downregulated and six upregulated in OM. A spot consistently overexpressed in odontogenic myxoma, with a molecular weight of 44-kDa and a pI of 3.5 was identified as the orosomucoid 1 protein. Western blot experiments confirmed the overexpression of this protein in odontogenic myxoma and immunohistochemical assays showed that this protein was mainly located in the cytoplasm of stellate and spindle-shaped cells of this neoplasm.


Orosomucoid 1, which belongs to a group of acute-phase proteins, may play a role in the modulation of the immune system and possibly it influences the development of OM.


  • Odontogenic myxoma
  • Dental follicle
  • Proteomic analysis
  • Orosomucoid 1
  • α1 acid glycoprotein


Odontogenic Myxoma (OM) is a relatively rare, benign neoplasm occurring in the jaws. This neoplasm is characterized by the presence of stellate and spindle-shaped cells embedded in an abundant myxoid or mucoid extracellular matrix. OM represents 3-20% of all odontogenic tumours and, in most studies, OM is the third most frequent odontogenic tumor [1]. Conservative surgery by enucleation and curettage is recommended when lesions of OM are smaller than 3 cm, but a segmental resection with immediate reconstruction is preferred in patients affected by bigger tumors [2].

OM as well as Dental Follicle (DF), an odontogenic tissue surrounding the enamel organ, and the dental papilla of the developing tooth germ prior to eruption [3], is derived from ectomesenchymal/mesencyhmal elements. Thus, OM could be mimicked by DF and dental papilla, both containing myxoid areas [46]. Indeed, a pathologist who is not familiar with the histology of a tooth germ can mistake a myxoid DF for an OM [6].

Up to now there are few studies comparing molecules of OM with other odontogenic mesenchymal tissues. Some authors compared the expression of α-SMA, S-100 and vimentin between OM and other mesenchymal tissues [7, 8], but not substantial differences were found. Another study described that the hyaluronic acid concentration in OM is four times higher than that of other glycosaminoglycans, such as chondroitin sulphate, which is inversely found in mesenchymal tissues from dental pulp, gingival and periodontal ligament, but not in DF [9]. It was also reported that 90% of OM cells expressed the metalloproteinase 2 (MMP-2), while only 10% of the cells in DF and myxoid dental pulp expressed this protein [10]. These authors also showed an increased expression of Bcl-2 and Bcl-x in OM. However, other studies reported less than 1% of Bcl-2 positive cells in OM [11, 12]. Finally, some works have been focused on the histological changes that occur in the hyperplastic DF and normal DF of impacted third molars and their histological association to OM and the possibilities of misinterpretation as OM [4, 6, 13, 14].

In recent years, the use of high-throughput genomics and proteomics has expanded rapidly in biomedical science. These technologies have evolved and make possible several discoveries in clinical cancer research, including the identification of biomarkers, molecular classification of tumors, molecular prediction of metastasis, treatment response, and prognosis. Particularly, the study of the proteome, the collection of all the proteins expressed from specific cells in all isoforms, polymorphisms and post-translational modifications [15], has allowed the detection of new biomarkers in diverse types of neoplasitic tissues, for example in urinary bladder cancer [16], ovarian carcinomas [17], oral squamous cell carcinoma [18], and lung cancer [19]. However, in the literature we have not found any previous study about OM or other odontogenic tumors using this approach.

To identify some proteins that could participate in the biological behavior of OM, in this work we used the proteomic technology based on 2-dimensional electrophoresis (2DE) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for comparing odontogenic myxoma (neoplastic) versus dental follicle (normal) tissues. A spot consistently overexpressed in odontogenic myxoma was identified as the orosomucoid 1 protein, which was located in the cytoplasm of the tumor cells.


Protein profiles of OM and DF

To identify proteins with differential expression in OM with respect to DF, the protein extracts from five OM (Table1) and five DF samples were analyzed by 2-DE using a wide range ampholyte pH 3–10 and profiles were visualized by colloidal Coomassie Blue G-250 staining. To minimize gel to gel variation, two-dimensional gels for each sample were realized at least twice. Both, DF and OM samples showed similar protein profiles, including more than 100 spots with molecular masses ranging from >170 to 5 kDa and pI values between 3 and 10 (Figure1A, B). Several protein spots consistently displayed significant differences in expression between OM and DF. Figure1 shows representative 2-DE of OM and DF with spots subjected to mass spectrometry and their identification numbers; the identified spots are listed in Table2.
Table 1

Details of cases




Approximate evolution

Approximate diameter





8 Months

3 × 2 cm/with expanded cortical

Increased volume/asymptomatic




12 Months

4 × 2 cm/with expanded cortical

Increased volume/paresthesia




3 Months

4 × 5 cm/with expanded cortical

Increased volume/asymptomatic




7 Months

9 × 5 cm/with expanded cortical

Increased volume/asymptomatic




3-5 years

4 × 5 cm/with expanded cortical

Increased volume/little pain

Figure 1
Figure 1

2DE protein profiles of Odontogenic Myxoma (OM) and Dental Follicle (DF) and identification of ORM1. Proteins from DF and OM were extracted and separated in 2DE. Then, gels were stained with Colloidal Coomassie Blue G-250. (A) Protein profile of OM. (B) Protein profile of DF. Proteins differentially expressed between both samples are numbered and one of the spots that consistently showed significant upregulation in OM is indicated by a frame. Under each gel are shown the magnifications and differential intensity analyses for the spot indicated by the frame. (C) This spot was excised from gels and subsequently analyzed by LC-MS/MS. This analysis identified this spot as the orosomucoid 1 protein (ORM1), which amino acid sequence is shown. The peptides identified by LC-MS/MS are underlined.

Table 2

Identification of proteins with differential expression in Odontogenic Myxoma

Spot ID



Theoretical Protein ID Mass KDa/pl

Mascot Score

Sequence Coverage

Major functions

Up-regulated proteins







Acute phase with inflammatory and immunomodulating properties







Molecular chaperone and cell signalling



Tropomyosin alpha-4




Calcium binding and acti-binding



14-3-3 protein




Cell signaling, cycle control, apoptosis and metabolism



Apolipoprotein A-1




Lipid transport, metabolism, apoptosis and autophagy



Serum Albumin in a Complex With Myristic Acid And Tri-lodobenzoic Acid




Protein of binding to cations, fatty acids, bilirubin and other

Down-regulated proteins



Glutathione S-transferase




Detoxify endogenous and environmental substances



Carbonic anhydrase 1




Ubiquitous metalloenzyme; bone resorption, calcification, ion transport, acid–base transport and metabolic processes

Accession numbers are from the MASCOT database (

Identification of orosomucoid-1 (ORM1)

One spot that consistently showed significant upregulation in OM was a molecule of approximately 44 kDa with a pI value around of 3.5 (Figure1, square). The results of the data query from the LC-MS/MS analysis indicated that four mass values of this spot matched with a human protein called orosomucoid 1 (ORM1), or alpha 1 acid glycoprotein, with a sequence coverage of 20.3% (Figure1C).

Expression of ORM1 in Odontogenic Myxoma vs Dental Follicle

To verify the differential expression of ORM1, which could play important functional roles in the development of OM, we performed Western blot assays on independent samples of OM and DF with a commercial monoclonal antibody. This analysis showed that the antibody strongly recognized a band of approximately 44 kDa, the expected molecular weight for the ORM1 protein, in all samples of OM analyzed, whereas this band was detected with minor intensity in samples of DF (Figure2). A 42-kDa band with roughly similar intensity was detected in all samples by an anti-actin antibody, used as internal control (Figure2). We performed densitometric analysis of the bands detected by those antibodies and the relative expression of ORM1 in a DF sample was arbitrarily taken as 1. This analysis showed that compared with DF, OM presented from 4.5- to 15-fold increased expression of ORM1 (Figure2). This result confirmed that ORM1 is highly expressed in OM.
Figure 2
Figure 2

Western blot assays for detection of the ORM 1 protein. Protein extracts from OM and DF samples were separated by PAGE-SDS and submitted to Western blot assays using antibodies against ORM1 and against actin, the latter used as an internal control. Relative intensities of the bands recognized by the antibodies were documented and analyzed by densitometry. The relative expression of ORM1 in a DF sample was arbitrary taken as 1.

Expression pattern of ORM1 in Odontogenic Myxoma vs normal Dental Follicle

To determine the in situ expression of ORM1 in the tumoral mass of OM, we performed an immunohistochemical assay on fourteen OM and ten DF samples using the monoclonal antibody against this protein. OM displayed positive cytoplasmic staining in majority of the stellate and spindle-shaped cells in all the analyzed samples (Figure3A, B), while mesenchymal cells of DF did not exhibit immunopositivity (Figure3C, D). In addition, in both tissues (OM and DF) the endothelial cells of large and small blood vessels showed ORM1 positivity (Figure3A-D). Positivity was also found in contaminant epithelial cells of DF (Figure3D).
Figure 3
Figure 3

In situ expression of ORM1 in OM and DF. Tissue sections from different samples of OM (A, B) and DF (C, D) were incubated with a monoclonal antibody against ORM1, then, with a biotinylated antimouse antibody, and finally with the streptavidine/peroxidase complex. The reaction products were visualized by the incubation with 3,3´-diaminobenzidine-H2O2 substrate. Finally, samples were analyzed by optic microscopy (20X). Insets show magnifications (40X) of the marked areas. Arrows indicate endothelial cells of blood vessels (B-D). Panel D also showed contaminant epithelial cells positive for ORM1.


The pathogenesis and source of OM is still controversial. Some authors have proposed an odontogenic origin, particularly from the dental follicle or from the periodontal ligament [20, 21]. Other authors have suggested that OM may be the result of a myxoid change in a pre-existing mesenchymal lesion or that it may represent a degenerative form of odontogenic fibroma [22]. In contrast, some authors have posed that the OM has a myofibroblastic origin [23, 24]. Nevertheless, in the last years many studies have compared the biochemical composition, particularly in the extracellular matrix, of OM with organs (dental pulp, dental follicles, gingival tissue and periodontal ligament) of a developing tooth [11, 25, 26]. The results obtained in the present study showed that the protein profiles of OM and DF are very similar; supporting the notion that OM could originate from DF.

To analyze proteins differentially expressed in OM and DF we used a proteomic approach based on 2-DE and peptide mass fingerprint by LC-MS/MS. This proteomic analysis revealed the variation of eight proteins identified (Table1).

Expression of carbonic anhydrase I (CA I) and glutathione S-transferase (GST) was downregulated in OM. Carbonic anhydrases catalyze the hydration of carbon dioxide and forms bicarbonate. CA I not only enhances the hydration reaction of CO2, but it also promotes the combining of bicarbonate with calcium to form the solid precipitant of calcium carbonate [27], a principal component of bones. Although OM is considered a benign neoplasm, it shows a high potential for bone resorption [28]. Thus, downregulation of CA I may affect the balance between bone resorption and apposition. On the other hand, GSTs are a large family of enzymes that catalyze the conjugation of reduced glutathione through a sulfhydryl group to electrophilic sites on a wide variety of substrates that could lead to the generation of reactive oxygen species (ROS) [29]. The products of GST catalysis are more water soluble, promoting ROS detoxification and thereby protecting tissues from oxidative damage. Thus, GST could be acting as a caretaker protein by protecting cells against genome damage induced by carcinogens and as a tumor-suppressor protein leading to tumor growth when inactivated [30]. It is, therefore, speculative that downexpression of GST in OM would lead to genome damage accumulation and be further injurious to the oral tissue.

A glucose-regulated protein (GRP94), albumin in a complex with myristic acid and tri-iodobenzoic acid, the tropomyosin alpha-4, the 14-3-3 protein zeta/delta, the apolipoprotein A-I, and the orosomucoid-1 protein were up-regulated in OM. Interestingly, overexpression of tropomyosin alpha-4 was also detected in esophageal squamous cell carcinoma [31], although their participation in tumor development remains to be investigated.

GRPs refer to a set of endoplasmic reticulum (ER) chaperones that have multiple functions in maintaining cellular homeostasis [32]. The endoplasmic reticulum stress pathways and the GRPs have been linked to cancer growth and drug resistance [33]. GRPs represent novel markers for cancer progression and chemo-responsiveness, as well as targets for cancer therapy. GRP94, also known as gp96, is the most abundant glycoprotein in ER and its overexpression associates with cellular transformation, tumorigenicity and decreased sensitivity to X-rays, whereas suppression of GRP94 sensitizes cells to etoposide treatment [32].

The 14-3-3 proteins belong to a family consisting of highly conserved acidic proteins with molecular weights of 25–30 kDa. They participate in phosphorylation-dependent protein-protein interactions that control progression through the cell cycle, initiation and maintenance of DNA damage checkpoints, activation of MAP kinases, prevention of apoptosis and coordination of integrin signaling and cytoskeletal dynamics [34]. Accumulating evidence now supports the concept that either an abnormal state of 14-3-3 protein expression, or dysregulation of 14-3-3/client protein interactions, contributes to the development of a large number of human diseases. In particular, clinical investigations in the field of oncology have demonstrated a correlation between upregulated 14-3-3 levels and poor survival of cancer patients [35].

ApoA-I is the major protein in HDL and plays an important role in reverse cholesterol transport by extracting cholesterol and phospholipids from peripheral cells and transferring it to the liver for excretion. In addition to its antiatherogenic properties, apoA-I also possesses anti-inflammatory and antioxidant properties [36]. Decreased levels of Apolipoprotein were found in a variety of cancer [3739], but such as in OM, Apolipoprotein A-I was increased in breast cancer and brain metastases in lung cancer [40, 41]. This controversy about the regulation of ApoA-I in cancer cells needs to be clarified in future studies.

By proteomics,Western blot and immunohistochemical assays, in the present study we showed that the ORM1 protein is overexpressed in OM. Interestingly, the same strategies allowed the identification of increased levels of ORM1 in urine samples of patients with urinary bladder cancer [16]. Moreover, increased levels of ORM1 have been reported in the sera of patients with different malignant diseases, including squamous cell carcinoma of head and neck [4246].

ORM1 belongs to a group of acute-phase proteins found in plasma. Such proteins undergo dramatic changes in concentration as a response of the organism to a disturbance of its homeostasis. These plasmatic proteins constitute a group of serum factors related to different immunological regulator functions and they have also been associated with tumor development and growth. However, it is uncertain whether the serum levels of acute-phase proteins, such as ORM1, increase as a response of the host to tumor growth or as a consequence of neoplastic cell production.

Human hepatocytes are normally the site of ORM1 production, but endothelial cells and some tumor cells can also produce it [16, 45, 47]. Additionally, some studies have shown that ORM1 is synthesized by lymphocytes, granulocytes, macrophages and monocytes [48, 49]. In the present study the expression of ORM1 in OM was mainly detected in the cytoplasm of stellate and spindle-shaped cells. However, this protein was also detected in the endothelial cells of blood vessels in both OM and DF tissue samples. It has been reported that ORM1 alone enhances migration but not the proliferation of human dermal microvascular endothelial cells, but in the presence of ORM1 and the vascular endothelial growth factor A (VEGF-A) the endothelial cells are capable to induce the development of endothelial tubes, suggesting that ORM1 seems to be involved in the regulation of angiogenesis [50]. Irmak et al. [16] proposed that the highest increase of ORM1 levels in advanced stages of urinary bladder cancer, which correspond to a vascularized tumor, could be due in part to the production of this protein by the augmented number of endothelial cells of angiogenically active blood vessels. The pro-angiogenic collaborative property of ORM1 may possibly occur in OM, but further studies with the association of angiogenic markers and ORM1 in OM are needed to test this hypothesis.

The presence of ORM1 in odontogenic myxoma also suggests a possible immunomodulatory function and a role in the growth and invasion potential of the tumoral cells. ORM1 is able to inhibit polymorphonuclear neutrophil activation and is considered a natural anti-inflammatory, anti-neutrophil, anti-complement and immunomodulatory agent [51]. Thus, the overexpression of ORM1 in OM may inhibit the immune response, resulting in an increase of tumor cell proliferation. Alternatively, the high expression of ORM1 in OM could represent a defense mechanism against proliferation and invasion of the tumor cells, similar to what occurs in colon cancer cells. In the latter neoplastic cells, the overexpression of ORM1 results in a reduced colony-forming capacity, as well as in a decrease of invasion and adhesion, whereas the inhibition of the expression of ORM1 by antisense oligodeoxynucleotides produces an increase of these events [52]. However, due to the multiple roles that have been described for ORM1 [51], it is difficult at this moment to assign just one specific function of this protein in OM.

On the other hand, ORM1 has very high carbohydrate content (45%). Glycoproteins contain carbohydrate residues from less than 1% until 80% of their total molecular weight and when glycoproteins include more than 4% of carbohydrates they are often called mucoproteins, because they have a high viscosity [53]. Macroscopically OM is an infiltrative mass of mucoid or slimy material, with a high viscosity. It is a slow growing tumor consisting of an accumulation of mucoid ground substance and, in some instances this mucoid mass can be infiltrative and destructive. The presence of ORM1 in OM possibly can justify the classical mucoid appearance of this tumor. However, in the immunohistochemical assays we only observed a cytoplasmic expression of this protein, whereas extracellular expression was not detected.


Our results showed that protein profiles of OM and DF are very similar, supporting the hypothesis that OM could originate from DF. We also identified eight proteins with differential expression between these samples. By Western blot and immunochemistry we confirmed the overexpression of the ORM1 protein in OM. This protein was located in the cytoplasm of stellate and spindle-shaped cells of OM as well as in the endothelial cells of large and small blood vessels. The properties and functions of ORM1 in this tumor are not clear, although the current evidence suggests possible immunomodulatory and/or angiogenic properties of this glycoprotein in the biological behavior of OM.


Tissue samples

Tissue samples were provided from the Department of Maxillofacial Surgery of the Juarez Hospital in Mexico City. The protocol was approved by the institutional committee of research and ethics under the registration number HJM 1996/11.03.08. For proteomics and Western blot analysis a total of five cases of OM diagnosed during the period between 2009 and 2011 were used in this work (Table1), as well as five samples of DF, the latter used as control tissues. Besides to the samples previously described, for immunolocalization assays of ORM1 we added nine OM and five DF samples, previously fixed in 10% neutral formalin and paraffin-embedded, which were obtained from the service of Maxillofacial Surgery of the Hospital Juarez de México and from Universidad de la República (UDELAR) Uruguay.

Tissue preparation

DF were separated from the mineralized tooth or extracted from alveolar bone in the routine extraction of the third molars from 16–20 year-old people. Then, samples were cleaned using physiological solution, introduced to liquid nitrogen and stored at −70°C until use. OM specimens were removed during surgery, cleaned with physiological solution, frozen in liquid nitrogen and stored at −70°C. In addition, paraffin-embedded sections of eleven OM and five DF samples were examined by immunohistochemical assays.

Protein extraction

Protein extraction of DF and OM was based on the selective extraction method described by Gorg et al. [54] and Perez et al. [55] with minor modifications. Briefly, samples were rinsed in physiological solution, frozen in liquid nitrogen, mechanically pulverized and suspended (400 mg tissue/ml) in sample buffer (7 M urea, 2 M tiourea, 4% CHAPS, 2% IPG buffer, 40 mM DTT) containing complete™ protease inhibitor cocktail (Roche, Germany). Then, samples were disrupted by sonication. Insoluble material was removed by centrifugation (20,000 xg for 5 min at 4°C), and the supernatant was preserved. Additionally, proteins were precipitated with acetone-TCA and the 2D Clean-Up Kit (Amersham Biosciences, USA). The precipitate was diluted in rehydration solution (7 M urea, 2 M thiourea, 2% CHAPS, 0.5%, IPG buffer and 0.1% bromophenol blue) supplemented with 2 mM DTT. Protein concentration was measured using 2D Quant Kit (Amersham Biosciences, USA) according to the manufacturer’s recommendations.

Two dimensional electrophoresis (2-DE)

Protein extracts suspended in rehydration solution (250 μl) were used to rehydrate Immobiline Drystrip Gels, pH 3–10 of 13 cm (GE Healthcare, USA) for 18 h at room temperature. Electrofocusing was performed in an Ettan IPGphor 3 Isoelectric Focusing System (GE Healthcare, USA) at 16–20 kVh for 5 h. Then, the immobilized pH gradient (IPG) strips were incubated for 10 min in reducing and alkylating 2-DE equilibration buffer (6 M urea, 75 mM Tris–HCl, pH 8.8, 29.3% glycerol, 2% sodium dodecyl sulfate and 0.1% bromophenol blue) plus 65 mM DTT and 135 mM iodoacetamide, successively. For SDS-polyacrylamide gel electrophoresis (SDS-PAGE), a standard vertical electrophoresis system was used with 10% polyacrylamyde gels (15 cm × 13 cm) in a Gibco BRL V16 gel system. Gels were stained with Colloidal Coomassie Blue G-250 (Bio-Safe Coomassie Stain, Bio-Rad Laboratories, USA). A digital image of the gels was obtained using scanning densitometry (Image Scanner, Amersham Biosciences, USA) and analyzed with Image Master 2D Platinum software, version 7.0 (GE Healthcare Life Sciences, Switzerland).

Identification of overexpressed proteins in OM

Six spots consistently overexpressed and two underexpressed in OM were excised, subjected to in-gel tryptic digestion and analyzed by LC-MS/MS [56]. Peptide mass fingerprinting and MS/MS data were searched against the human genome database using the MASCOT 2.1 program ( allowing a monoisotopic mass tolerance of 1 Da. Methionine oxidation and one missed tryptic cleavage were used during the database search.

Western blot

Western blot assays were performed as previously described [57]. Briefly, proteins in rehydration solution were separated by 10% SDS-PAGE and transferred to nitrocellulose membranes. After blocking for 2 h in 5% nonfat milk in Tris-buffered saline (TBS) containing 0.05% Tween-20, membranes were incubated with a monoclonal antibody against the orosomucoid 1 protein (ORM1) (1:5000) (Abcam, UK) and then with an anti-mouse secondary antibody conjugated to horseradish peroxidase (Invitrogen, USA) (1:10,000). As internal control, samples were probed with antibodies against α-actin (kindly provided by Dr. Manuel Hernández-Hernández, CINVESTAV-IPN). Antibody detection was developed by chemioluminescence (ECL, GE Healthcare Life Sciences, Switzerland). Relative intensities were documented and analyzed by densitometry.

Histopathology and Immunohistochemical staining

OM and DF specimens were fixed in 10% buffered formalin and embedded in paraffin. Tissue sections of 2 μm thick were obtained and stained with hematoxylin and eosin, under standard procedures. All slides were reviewed for histopathological classification of odontogenic tumors according to the recent classification of head and neck tumors of the World Health Organization [1].

For immunohistochemical studies, tissue sections from fourteen OM and ten DF samples were treated with 0.1 M sodium citrate (pH 6.2) and Tween-20 for the unraveling of the epitopes. Endogenous peroxidases were blocked with 0.9% hydrogen peroxide, followed by incubation with 1% BSA in PBS for 5 min, in order to eliminate non-specific binding. Then, samples were incubated with monoclonal antibodies against ORM1 (1:200), and then with a biotinylated anti-mouse antibody, and finally with the streptavidine/peroxidase complex (LSAB + Labeled streptavid-Biotin, Dako Corporation, USA). The reaction products were visualized by incubation with 3,3´-diaminobenzidine-H2O2 as substrate (Dako Corporation, USA). Sections were counterstained with Mayer´s hematoxylin solution and visualized by optical microscopy. As a negative control, PBS was applied to substitute the primary antibody.



Two-dimensional electrophoresis


Dental follicle


Immobilized pH gradients


Liquid chromatography-tandem mass spectrometry


Odontogenic myxoma


Orosomucoid 1 protein


SDS-polyacrylamide gel electrophoresis.



This work was supported by Instituto de Ciencia y Tecnología del Distrito Federal (ICyTDF, Mexico) and Consejo Nacional de Ciencia y Tecnología (CONACyT, Mexico). We thank Leticia Cortes-Martinez for her invaluable technical assistance.

Authors’ Affiliations

Departamento de Infectómica y Patogénesis Molecular, CINVESTAV-IPN, México, D.F., México
Departamento de Investigación, Escuela de Odontología, Universidad Juárez del Estado de Durango, Durango, México
Facultad de Odontología, Universidad de la República (UDELAR), Montevideo, Uruguay
Laboratorio de Patología Molecular, Instituto Nacional de Pediatría, México, D.F., México
Departamento de Cirugía Maxilofacial, Hospital Juárez de México, México, D.F., México
Departamento de Bioquímica, Facultad de Medicina, UNAM, México, D.F., México


  1. Buchner A, Odell E: Odontogenic myxoma/myxofibroma. In Head and neck tumours Pathology and genetics WHO Classification of tumours. Edited by: Barnes L, Eveson J, Reichart P, Sidransky D. IARC Press, Lyon; 2005:316.Google Scholar
  2. Boffano P, Gallesio C, Barreca A, Bianchi FA, Garzino-Demo P, Roccia F: Surgical treatment of odontogenic myxoma. J Craniofac Surg 2011, 22: 982–987. 10.1097/SCS.0b013e3182101400View ArticlePubMedGoogle Scholar
  3. Huang GT, Gronthos S, Shi S: Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res 2009, 88: 792–806. 10.1177/0022034509340867View ArticlePubMedGoogle Scholar
  4. Suarez PA, Batsakis JG, El-Naggar AK: Don't confuse dental soft tissues with odontogenic tumors. Ann Otol Rhinol Laryngol 1996, 105: 490–494.View ArticlePubMedGoogle Scholar
  5. Muller H, Slootweg PJ: A peculiar complication in Le Fort I osteotomy. J Craniomaxillofac Surg 1988, 16: 238–239.View ArticlePubMedGoogle Scholar
  6. Kim J, Ellis GL: Dental follicular tissue: misinterpretation as odontogenic tumors. J Oral Maxillofac Surg 1993, 51: 762–767. discussion 767–768 10.1016/S0278-2391(10)80417-3View ArticlePubMedGoogle Scholar
  7. Lombardi T, Lock C, Samson J, Odell EW: S100, alpha-smooth muscle actin and cytokeratin 19 immunohistochemistry in odontogenic and soft tissue myxomas. J Clin Pathol 1995, 48: 759–762. 10.1136/jcp.48.8.759View ArticlePubMedGoogle Scholar
  8. Lombardi T, Samson J, Bernard JP, Di Felice R, Fiore-Donno G, Muhlhauser J, Maggiano N: Comparative immunohistochemical analysis between jaw myxoma and mesenchymal cells of tooth germ. Pathol Res Pract 1992, 188: 141–144. 10.1016/S0344-0338(11)81170-2View ArticlePubMedGoogle Scholar
  9. Mosqueda-Taylor A: New findings and controversies in odontogenic tumors. Med Oral Patol Oral Cir Bucal 2008, 13: E555-E558.PubMedGoogle Scholar
  10. Bast BT, Pogrel MA, Regezi JA: The expression of apoptotic proteins and matrix metalloproteinases in odontogenic myxomas. J Oral Maxillofac Surg 2003, 61: 1463–1466. 10.1016/j.joms.2003.06.002View ArticlePubMedGoogle Scholar
  11. Martinez-Mata G, Mosqueda-Taylor A, Carlos-Bregni R, de Almeida OP, Contreras-Vidaurre E, Vargas PA, Cano-Valdez AM, Dominguez-Malagon H: Odontogenic myxoma: clinico-pathological, immunohistochemical and ultrastructural findings of a multicentric series. Oral Oncol 2008, 44: 601–607. 10.1016/j.oraloncology.2007.08.009View ArticlePubMedGoogle Scholar
  12. Iezzi G, Piattelli A, Rubini C, Artese L, Fioroni M, Carinci F: MIB-1, Bcl-2 and p53 in odontogenic myxomas of the jaws. Acta Otorhinolaryngol Ital 2007, 27: 237–242.PubMedGoogle Scholar
  13. Curran AE, Damm DD, Drummond JF: Pathologically significant pericoronal lesions in adults: Histopathologic evaluation. J Oral Maxillofac Surg 2002, 60: 613–617. discussion 618 10.1053/joms.2002.33103View ArticlePubMedGoogle Scholar
  14. Kotrashetti VS, Kale AD, Bhalaerao SS, Hallikeremath SR: Histopathologic changes in soft tissue associated with radiographically normal impacted third molars. Indian J Dent Res 2010, 21: 385–390. 10.4103/0970-9290.70809View ArticlePubMedGoogle Scholar
  15. Graham DR, Elliott ST, Van Eyk JE: Broad-based proteomic strategies: a practical guide to proteomics and functional screening. J Physiol 2005, 563: 1–9.View ArticlePubMedGoogle Scholar
  16. Irmak S, Tilki D, Heukeshoven J, Oliveira-Ferrer L, Friedrich M, Huland H, Ergun S: Stage-dependent increase of orosomucoid and zinc-alpha2-glycoprotein in urinary bladder cancer. Proteomics 2005, 5: 4296–4304. 10.1002/pmic.200402005View ArticlePubMedGoogle Scholar
  17. Wang Q, Li D, Zhang W, Tang B, Li QQ, Li L: Evaluation of proteomics-identified CCL18 and CXCL1 as circulating tumor markers for differential diagnosis between ovarian carcinomas and benign pelvic masses. Int J Biol Markers 2011, 26: 262–273.PubMedGoogle Scholar
  18. Hu S, Arellano M, Boontheung P, Wang J, Zhou H, Jiang J, Elashoff D, Wei R, Loo JA, Wong DT: Salivary proteomics for oral cancer biomarker discovery. Clin Cancer Res 2008, 14: 6246–6252. 10.1158/1078-0432.CCR-07-5037View ArticlePubMedGoogle Scholar
  19. Taguchi A, Politi K, Pitteri SJ, Lockwood WW, Faca VM, Kelly-Spratt K, Wong CH, Zhang Q, Chin A, Park KS, et al.: Lung cancer signatures in plasma based on proteome profiling of mouse tumor models. Cancer Cell 2011, 20: 289–299. 10.1016/j.ccr.2011.08.007View ArticlePubMedGoogle Scholar
  20. Schneider LC, Weisinger E: Odontogenic fibromyxoma arising from the periodontal ligament. J Periodontol 1975, 46: 493–497.View ArticlePubMedGoogle Scholar
  21. Lucas R, Pindborg J: Odontogenic tumors and tumor-like lesions. Scientific foundations of dentistry, London; 1976.Google Scholar
  22. Adekeye EO, Avery BS, Edwards MB, Williams HK: Advanced central myxoma of the jaws in Nigeria. Clinical features, treatment and pathogenesis. Int J Oral Surg 1984, 13: 177–186. 10.1016/S0300-9785(84)80001-0View ArticlePubMedGoogle Scholar
  23. Moshiri S, Oda D, Worthington P, Myall R: Odontogenic myxoma: histochemical and ultrastructural study. J Oral Pathol Med 1992, 21: 401–403. 10.1111/j.1600-0714.1992.tb01027.xView ArticlePubMedGoogle Scholar
  24. Hasleton PS, Simpson W, Craig RD: Myxoma of the mandible–a fibroblastic tumor. Oral Surg Oral Med Oral Pathol 1978, 46: 396–406. 10.1016/0030-4220(78)90405-XView ArticlePubMedGoogle Scholar
  25. Schmidt-Westhausen A, Becker J, Schuppan D, Burkhardt A, Reichart PA: Odontogenic myxoma–characterisation of the extracellular matrix (ECM) of the tumour stroma. Eur J Cancer B Oral Oncol 1994, 30B: 377–380.View ArticlePubMedGoogle Scholar
  26. Slootweg PJ, van den Bos T, Straks W: Glycosaminoglycans in myxoma of the jaw: a biochemical study. J Oral Pathol 1985, 14: 299–306. 10.1111/j.1600-0714.1985.tb00497.xView ArticlePubMedGoogle Scholar
  27. Supuran CT: Carbonic anhydrases–an overview. Curr Pharm Des 2008, 14: 603–614. 10.2174/138161208783877884View ArticlePubMedGoogle Scholar
  28. Noffke CE, Raubenheimer EJ, Chabikuli NJ, Bouckaert MM: Odontogenic myxoma: review of the literature and report of 30 cases from South Africa. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007, 104: 101–109. 10.1016/j.tripleo.2007.01.026View ArticlePubMedGoogle Scholar
  29. Hayes JD, Pulford DJ: The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 1995, 30: 445–600. 10.3109/10409239509083491View ArticlePubMedGoogle Scholar
  30. Karius T, Schnekenburger M, Ghelfi J, Walter J, Dicato M, Diederich M: Reversible epigenetic fingerprint-mediated glutathione-S-transferase P1 gene silencing in human leukemia cell lines. Biochem Pharmacol 2011, 81: 1329–1342. 10.1016/j.bcp.2011.03.014View ArticlePubMedGoogle Scholar
  31. Harada T, Kuramitsu Y, Makino A, Fujimoto M, Iizuka N, Hoshii Y, Takashima M, Tamesa M, Nishimura T, Takeda S, et al.: Expression of tropomyosin alpha 4 chain is increased in esophageal squamous cell carcinoma as evidenced by proteomic profiling by two-dimensional electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry. Proteomics Clin Appl 2007, 1: 215–223. 10.1002/prca.200600609View ArticlePubMedGoogle Scholar
  32. Fu Y, Lee AS: Glucose regulated proteins in cancer progression, drug resistance and immunotherapy. Cancer Biol Ther 2006, 5: 741–744. 10.4161/cbt.5.7.2970View ArticlePubMedGoogle Scholar
  33. Koumenis C, Wouters BG: "Translating" tumor hypoxia: unfolded protein response (UPR)-dependent and UPR-independent pathways. Mol Cancer Res 2006, 4: 423–436. 10.1158/1541-7786.MCR-06-0150View ArticlePubMedGoogle Scholar
  34. Morrison DK: The 14–3-3 proteins: integrators of diverse signaling cues that impact cell fate and cancer development. Trends Cell Biol 2009, 19: 16–23. 10.1016/j.tcb.2008.10.003View ArticlePubMedGoogle Scholar
  35. Zhao J, Meyerkord CL, Du Y, Khuri FR, Fu H: 14–3-3 proteins as potential therapeutic targets. Semin Cell Dev Biol 2011, 22: 705–712. 10.1016/j.semcdb.2011.09.012View ArticlePubMedGoogle Scholar
  36. Tardif JC, Heinonen T, Noble S: High-density lipoprotein/apolipoprotein A-I infusion therapy. Curr Atheroscler Rep 2009, 11: 58–63. 10.1007/s11883-009-0009-7View ArticlePubMedGoogle Scholar
  37. Kozak KR, Su F, Whitelegge JP, Faull K, Reddy S, Farias-Eisner R: Characterization of serum biomarkers for detection of early stage ovarian cancer. Proteomics 2005, 5: 4589–4596. 10.1002/pmic.200500093View ArticlePubMedGoogle Scholar
  38. Engwegen JY, Helgason HH, Cats A, Harris N, Bonfrer JM, Schellens JH, Beijnen JH: Identification of serum proteins discriminating colorectal cancer patients and healthy controls using surface-enhanced laser desorption ionisation-time of flight mass spectrometry. World J Gastroenterol 2006, 12: 1536–1544.PubMedGoogle Scholar
  39. Ehmann M, Felix K, Hartmann D, Schnolzer M, Nees M, Vorderwulbecke S, Bogumil R, Buchler MW, Friess H: Identification of potential markers for the detection of pancreatic cancer through comparative serum protein expression profiling. Pancreas 2007, 34: 205–214. 10.1097/01.mpa.0000250128.57026.b2View ArticlePubMedGoogle Scholar
  40. Huang HL, Stasyk T, Morandell S, Dieplinger H, Falkensammer G, Griesmacher A, Mogg M, Schreiber M, Feuerstein I, Huck CW, et al.: Biomarker discovery in breast cancer serum using 2-D differential gel electrophoresis/MALDI-TOF/TOF and data validation by routine clinical assays. Electrophoresis 2006, 27: 1641–1650. 10.1002/elps.200500857View ArticlePubMedGoogle Scholar
  41. Marchi N, Mazzone P, Fazio V, Mekhail T, Masaryk T, Janigro D: ProApolipoprotein A1: a serum marker of brain metastases in lung cancer patients. Cancer 2008, 112: 1313–1324. 10.1002/cncr.23314View ArticlePubMedGoogle Scholar
  42. van Gool J, van Vugt H, Helle M, Aarden LA: The relation among stress, adrenalin, interleukin 6 and acute phase proteins in the rat. Clin Immunol Immunopathol 1990, 57: 200–210. 10.1016/0090-1229(90)90034-NView ArticlePubMedGoogle Scholar
  43. Stanciu L, Dumitrascu D, Radu D, Badea R: Non-specific tumoral markers in hepatocellular carcinoma. Med Interne 1990, 28: 139–144.PubMedGoogle Scholar
  44. Tosner J, Krejsek J, Louda B: Serum prealbumin, transferrin and alpha-1-acid glycoprotein in patients with gynecological carcinomas. Neoplasma 1988, 35: 403–411.PubMedGoogle Scholar
  45. Croce MV, Price MR, Segal-Eiras A: Association of a alpha1 acidic glycoprotein and squamous cell carcinoma of the head and neck. Pathol Oncol Res 2001, 7: 111–117. 10.1007/BF03032576View ArticlePubMedGoogle Scholar
  46. Croce MV, Segal-Eiras A: Identification of acute-phase proteins (APP) in circulating immune complexes (CIC) in esophageal cancer patients' sera. Cancer Invest 1996, 14: 421–426. 10.3109/07357909609018899View ArticlePubMedGoogle Scholar
  47. Sorensson J, Matejka GL, Ohlson M, Haraldsson B: Human endothelial cells produce orosomucoid, an important component of the capillary barrier. Am J Physiol 1999, 276: H530-H534.PubMedGoogle Scholar
  48. Gahmberg CG, Andersson LC: Leukocyte surface origin of human alpha1-acid glycoprotein (orosomucoid). J Exp Med 1978, 148: 507–521. 10.1084/jem.148.2.507View ArticlePubMedGoogle Scholar
  49. Andersson LC, Gahmberg CG: Surface glycoproteins of resting and activated human T lymphocytes. Mol Cell Biochem 1979, 27: 117–131.View ArticlePubMedGoogle Scholar
  50. Irmak S, Oliveira-Ferrer L, Singer BB, Ergun S, Tilki D: Pro-angiogenic properties of orosomucoid (ORM). Exp Cell Res 2009, 315: 3201–3209. 10.1016/j.yexcr.2009.07.024View ArticlePubMedGoogle Scholar
  51. Fournier T, Medjoubi NN, Porquet D: Alpha-1-acid glycoprotein. Biochim Biophys Acta 2000, 1482: 157–171. 10.1016/S0167-4838(00)00153-9View ArticlePubMedGoogle Scholar
  52. Lee SY, Lim JW, Kim YM: Effect of alpha1-acid glycoprotein expressed in cancer cells on malignant characteristics. Mol Cells 2001, 11: 341–345.PubMedGoogle Scholar
  53. Lopez-Vidriero MT, Reid L: Chemical markers of mucous and serum glycoproteins and their relation to viscosity in mucoid and purulent sputum from various hypersecretory diseases. Am Rev Respir Dis 1978, 117: 465–477.PubMedGoogle Scholar
  54. Gorg A, Obermaier C, Boguth G, Harder A, Scheibe B, Wildgruber R, Weiss W: The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 2000, 21: 1037–1053. 10.1002/(SICI)1522-2683(20000401)21:6<1037::AID-ELPS1037>3.0.CO;2-VView ArticlePubMedGoogle Scholar
  55. Perez E, Gallegos JL, Cortes L, Calderon KG, Luna JC, Cazares FE, Velasquillo MC, Kouri JB, Hernandez FC: Identification of latexin by a proteomic analysis in rat normal articular cartilage. Proteome Sci 2010, 8: 27. 10.1186/1477-5956-8-27View ArticlePubMedGoogle Scholar
  56. Zimny-Arndt U, Schmid M, Ackermann R, Jungblut PR: Classical proteomics: two-dimensional electrophoresis/MALDI mass spectrometry. Methods Mol Biol 2009, 492: 65–91. 10.1007/978-1-59745-493-3_4View ArticlePubMedGoogle Scholar
  57. Lau AT, He QY, Chiu JF: A proteome analysis of the arsenite response in cultured lung cells: evidence for in vitro oxidative stress-induced apoptosis. Biochem J 2004, 382: 641–650. 10.1042/BJ20040224View ArticlePubMedGoogle Scholar


© Garcia-Muñoz et al.; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.