transforming-growth-factor-beta and Ameloblastoma

Ameloblastoma (AB) is the most common benign epithelial odontogenic tumor occurring in the jawbone. AB is a slowly growing tumor but sometimes shows a locally invasive and an aggressive growth pattern with a marked bone resorption. In addition, the local recurrence and distant metastasis of AB also sometimes occurs, which resembles one of the typical malignant potentials. From these points of view, to understand better the mechanisms of AB cell migration or invasion is necessary for the better clinical therapy and improvements of the patients' quality of life. Microtubules in eukaryotic cells reveal the shape of hollow cylinders made up of polymerized alpha (α)- and beta (β)-tubulin dimers and form the cytoskeleton together with microfilaments and intermediate filaments. Microtubules play important roles in cell migration by undergoing assembly and disassembly with post-translational modifications. Stability of microtubules caused by their acetylation is involved in cell migration. In this study, we investigated the expression and distribution of acetylated α-tubulin and alpha-tubulin N-acetyltransferase 1 (αTAT1), an enzyme which acetylates Lys-40 in α-tubulin, in AB specimens, and analyzed how tubulin was acetylated by αTAT1 activation in a human AB cell line, AM-1. Finally, we clarified that TGF-β-activated kinase1 (TAK1) was phosphorylated by TGF-β stimulation, then, induced tubulin acetylation via αTAT1 activation, which subsequently activated the migration and invasion of AB cells.

Topics: Acetylation; Acetyltransferases; Adolescent; Adult; Aged; Ameloblastoma; Cell Line, Tumor; Cell Movement; Female; Humans; Immunohistochemistry; Jaw Neoplasms; Male; MAP Kinase Kinase Kinases; Microtubule Proteins; Middle Aged; Neoplasm Invasiveness; RNA Interference; Transforming Growth Factor beta; Tubulin; Young Adult

Ameloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic malignant neoplasm and the malignant counterpart of benign epithelial odontogenic tumor of ameloblastoma (AB) by the WHO classification. AC develops pulmonary metastasis in about one third of the patients and reveals a poor prognosis. However, the mechanisms of AC oncogenesis remain unclear. In this report, we aimed to clarify the mechanisms of malignant transformation of AB or AC carcinogenesis. The relatively important genes in the malignant transformation of AB were screened by DNA microarray analysis, and the expression and localization of related proteins were examined by immunohistochemistry using samples of AB and secondary AC. Two genes of hypoxia-inducible factor 1 alpha subunit (HIF1A) and zinc finger E-box-binding homeobox 1 (ZEB1) were significantly and relatively upregulated in AC than in AB. Both genes were closely related in hypoxia and epithelial-mesenchymal transition (EMT). In addition, expressions of HIF-1α and ZEB1 proteins were significantly stronger in AC than in AB. In the cell assays using ameloblastoma cell line, AM-1, hypoxia condition upregulated the expression of transforming growth factor-β (TGF-β) and induced EMT. Furthermore, the hypoxia-induced morphological change and cell migration ability were inhibited by an antiallergic medicine tranilast. Finally, we concluded that hypoxia-induced HIF-1α and ZEB1 were critical for the malignant transformation of AB via TGF-β-dependent EMT. Then, both HIF-1α and ZEB1 could be potential biomarkers to predict the malignant transformation of AB.

Topics: Adolescent; Adult; Aged; Ameloblastoma; Cell Line, Tumor; Cell Transformation, Neoplastic; Epithelial-Mesenchymal Transition; Female; Gene Expression Profiling; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Male; Middle Aged; Transforming Growth Factor beta; Young Adult; Zinc Finger E-box-Binding Homeobox 1

Induction of podoplanin by transforming growth factor-β (TGF-β) has been shown in a number of lesions but not in odontogenic tumors (OTs). We evaluated the association between these markers in OTs for the first time and compared their expression among the different neoplasms.. Immunohistochemistry using monoclonal antibody against podoplanin and TGF-β was performed on 76 odontogenic cysts and tumors. Spearman's correlation coefficient, Kruskal-Wallis, and Mann-Whitney U tests followed by adjustment with Bonferroni were used for statistical analysis (P < .05).. A significant difference in podoplanin expression was found among the lesions consisting of solid ameloblastomas, adenomatoid odontogenic tumors, ameloblastic fibromas, odontogenic myxomas (OMs), odontogenic keratocysts, and calcifying odontogenic cysts. Significant differences were observed only between OMs and each of the other neoplasms. Podoplanin immunostaining in the connective tissue was absent in most lesions. TGF-β was significantly different among the study sample but not between the lesions in paired comparisons. None of the studied OTs showed significant correlations between podoplanin-TGF-β, in either the epithelium or the stroma. These markers were also descriptively reported in calcifying epithelial odontogenic tumors.. The inductive effect of TGF-β on podoplanin seems to be limited, if any, in odontogenic lesions. Podoplanin appears to play a role in some aspects of OTs with epithelial or mixed origins. Despite the possible participation of podoplanin in tumorigenesis, it may not necessarily be involved in the aggressive behavior of OTs.

Topics: Ameloblastoma; Carcinogenesis; Gene Expression; Genetic Association Studies; Humans; Immunohistochemistry; Membrane Glycoproteins; Myxoma; Odontogenic Cysts; Odontogenic Tumors; Odontoma; Signal Transduction; Transforming Growth Factor beta

Tumor parenchyma-stromal interactions affect the properties of tumors and their dynamics. Our group previously showed that secreted frizzled related protein (sFRP)-2 impairs bone formation and promotes bone invasion in ameloblastoma. However, the effects of the secreted growth factors CCN2, TGF-β, and BMP4 on stromal tissues in ameloblastoma remain unclear.. Thirty-five paraffin-embedded ameloblastoma cases, ameloblastoma-derived cell lines (AM-1), and primary cultures of ameloblastoma stromal fibroblasts (ASF) were used. Immunohistochemistry, MTT assay, Western blotting, and RT-PCR were performed on these samples. Parenchyma-stromal CCN2 overexpression correlated significantly with fibrous-type stroma, but not with myxoid-type stroma, suggesting a role of CCN2 in fibrosis (P < 0.05). Recombinant CCN2 induction of enhanced ASF proliferation in AM-1 medium supports this view. Conversely, BMP4 and TGF-β were expressed in myxoid-type fibroblasts, but little expression was found in parenchyma. RANKL-positive and CD68-positive stromal cell populations were significantly greater in myxoid-type tumor areas than in fibrous-type tumor areas, while a higher Ki-67 labeling index was recorded in ameloblastoma with fibrous-type stroma. These data suggest that stromal properties influence bone resorption-related activities and growth rates, respectively.. These results suggest that the effects of secreted growth factors are governed by ameloblastoma parenchyma-stromal interactions. CCN2 promotes fibrogenesis independent of TGF-β signaling. Absence of CCN2 expression is associated with a phenotypic switch to a myxoid-type microenvironment that is conducive for TGF-β/BMP4 signaling to promote osteoclastogenesis.

Topics: Adolescent; Adult; Aged; Ameloblastoma; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Bone Morphogenetic Protein 4; Bone Resorption; Cell Proliferation; Connective Tissue Growth Factor; Female; Fibroblasts; Fibrosis; Humans; Immunohistochemistry; Jaw Neoplasms; Male; Middle Aged; Osteogenesis; RANK Ligand; Stromal Cells; Transforming Growth Factor beta; Tumor Cells, Cultured; Young Adult

The number of studies investigating the immunohistochemical characteristics of glandular odontogenic cysts (GOCs) is limited, due to its rarity. TGF-beta has been suggested to induce podoplanin expression in some lesions. We aimed to evaluate and compare podoplanin and TGF-beta expression in GOC and other odontogenic cystic lesions.. A total of 43 samples including five GOCs, 10 dentigerous cysts (DCs), eight unicystic ameloblastoma (UAs), and 20 radicular cysts (RCs) were selected and subjected to immunohistochemical staining using monoclonal antibodies against podoplanin and TGF-beta. Kruskal-Wallis test and Mann-Whitney U-test were used for statistical analysis along with Bonferroni for adjusting P-values (P < 0.05).. Podoplanin immunoreactivity was observed in 80%, 70%, and 100% of DCs, RCs, and UAs, respectively, while none of the GOCs were positive for this marker (P = 0.004). Significant differences were only found in the GOC specimens. TGF-beta positivity occurred in the capsule and epithelium of all GOCs and DCs, while RCs and UAs demonstrated different expression percentages in the capsular and epithelial tissues. Epithelial TGF-beta showed significant differences among the studied lesions (P = 0.007) with the main difference found between DCs with RCs and DCs with UAs.. Lack of podoplanin expression might be involved in the characteristic histologic and behavioral features of GOC, which seems to be unrelated to TGF-beta expression.

Topics: Ameloblastoma; Dentigerous Cyst; Humans; Jaw Diseases; Jaw Neoplasms; Membrane Glycoproteins; Odontogenic Cysts; Radicular Cyst; Transforming Growth Factor beta

Ameloblastoma (AM) shows locally invasive behaviour. However, biological investigations regarding regulation of gene expression associated with AM pathological features are difficult to perform, because AM cells can be passaged for a few generations due to senescence. We report a newly established immortalized AM cell line, AMB cells, by transfection with human telomerase reverse transcriptase (hTERT). Furthermore, we examined whether TNF-α modulates bone resorption-related genes, IL-6 and MMP-9 in cooperation with TGF-β or IFN-γ.. Following transfection of an hTERT expression vector into AM cells using a non-viral method, the effects of cytokines on the expressions of IL-6 and MMP-9 mRNA were examined using real-time PCR. TNF-α-induced NF-κB activity was examined by western blotting and transcription factor assays.. AMB cells continued to grow for more than 100 population doublings. Stimulation with TNF-α increased IL-6 and MMP-9 mRNA expressions, as well as NF-κB activation. Furthermore, TGF-β and IFN-γ dramatically increased TNF-α-mediated expressions of MMP-9 and IL-6 mRNA, respectively, while those responses were suppressed by NF-κB inhibitor.. We established an immortalized AM cell line by hTERT transfection. TNF-α-mediated regulation of MMP-9 and IL-6 via NF-κB may play an important role in the pathological behaviour of AMs, such as bone resorption.

Topics: Adult; Ameloblastoma; Cell Line, Tumor; Cell Proliferation; Cellular Senescence; Female; Gene Expression; Humans; Interferon-gamma; Interleukin-6; Jaw Neoplasms; Matrix Metalloproteinase 9; NF-kappa B; Nitriles; RNA, Messenger; Sulfones; Telomerase; Transfection; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

The Fifth Biennial Research Summit of the American Association of Oral and Maxillofacial Surgeons and its Committee on Research Planning and Technology Assessment was held in Rosemont, Illinois on May 6 and 7, 2015. The goal of the symposium is to provide a forum for the most recent clinical and scientific advances to be brought to the specialty. The proceedings of the events of that summit are presented in this report.

Topics: Ameloblastoma; Bone Morphogenetic Protein 2; Bone Regeneration; Carcinogenesis; Congresses as Topic; Dental Research; Fibrous Dysplasia of Bone; Humans; Imaging, Three-Dimensional; Nerve Growth Factor; Odontogenic Tumors; Osteolysis; Patient Care Planning; Plastic Surgery Procedures; Printing, Three-Dimensional; Recombinant Proteins; Regenerative Medicine; Registries; Societies, Dental; Surgery, Computer-Assisted; Surgery, Oral; Tissue Engineering; Transforming Growth Factor beta; Translational Research, Biomedical; User-Computer Interface

Recombinant human morphogenetic protein (rhBMP) is a graft alternative for extensive mandibular reconstruction after tumor resections. However, the feasibility of rhBMP-2 to receive osseointegrated implants and prosthetic rehabilitation has been rarely reported. This study reports on a case of an extensive solid ameloblastoma along the mandibular body. The treatment consisted of resection followed by off-label use of rhBMP type 2 associated with bovine bone xenograft. Eleven months postoperatively, the patient was prosthetically rehabilitated with dental implants, without evidence of resorption or complications. The literature on mandibular reconstructions using rhBMP and their feasibility for future osseointegrated implant placement was also reviewed. Based on the presented case, the association between rhBMP-2 and a bovine bone xenograft could be considered a feasible option for the reconstruction and rehabilitation of large mandibular defects after tumor resection. According to the literature, the use of rhBMP as a graft material is encouraging, with good clinical outcome. However, there are no long-term studies demonstrating success and survival rates of implants placed in these grafts. Future investigations will be required to ascertain the long-term survival of implants in areas grafted with rhBMP. Also, there is a lack of information regarding the prosthetic rehabilitation of these patients.

Topics: Absorbable Implants; Adult; Ameloblastoma; Animals; Bone Morphogenetic Protein 2; Bone Transplantation; Cattle; Collagen; Dental Implantation, Endosseous; Dental Implants; Dental Prosthesis, Implant-Supported; Denture, Partial; Feasibility Studies; Follow-Up Studies; Heterografts; Humans; Male; Mandibular Neoplasms; Mandibular Reconstruction; Membranes, Artificial; Minerals; Osseointegration; Recombinant Proteins; Surgical Mesh; Transforming Growth Factor beta

Numerous autogenous bone-grafting procedures are available for the recovering of large continuity defects of the mandible. However, these surgical techniques present several limitations involving postoperative morbidity and pain. The development of new bone technique reconstruction not involving autogenous bone graft would offer new opportunities for facial bone reconstruction. This report highlights the possibility of recombinant human bone morphogenetic protein type 2 (rhBMP-2) application without concomitant bone grafting material in the restoration of continuity critical-sized defects after tumor resection in the mandible. The presented case shows a large mandibular reconstruction after tumor removal in a 31-year-old white man affected by ameloblastoma. In this case, the rhBMP-2 application with a carrier consisted on absorbable collagen sponge gives excellent newly formed bone at 18 months of control clinical and radiologic follow-up. The results indicated that the use of rhBMP-2 without concomitant autogenous bone grafting materials in large critical-sized mandibular defects secondary to large mandibular tumor produced excellent regeneration of the treated area.

Topics: Absorbable Implants; Adult; Allografts; Ameloblastoma; Bone Morphogenetic Protein 2; Bone Regeneration; Collagen; Drug Carriers; Follow-Up Studies; Humans; Male; Mandibular Neoplasms; Mandibular Reconstruction; Osteogenesis; Plastic Surgery Procedures; Recombinant Proteins; Surgical Mesh; Transforming Growth Factor beta

Large mandibular resection defects historically have been treated using autogenous bone grafts and reconstruction plates. However, a major drawback of large autogenous bone grafts is donor-site morbidity.. This report describes the replacement of a 10-cm anterior mandibular ameloblastoma resection defect, reproducing the original anatomy of the chin, using a tissue-engineered construct consisting of β-tricalcium phosphate (β-TCP) granules, recombinant human bone morphogenetic protein-2 (BMP-2), and Good Manufacturing Practice-level autologous adipose stem cells (ASCs). Unlike prior reports, 1-step in situ bone formation was used without the need for an ectopic bone-formation step. The reconstructed defect was rehabilitated with a dental implant-supported overdenture. An additive manufactured medical skull model was used preoperatively to guide the prebending of patient-specific hardware, including a reconstruction plate and titanium mesh. A subcutaneous adipose tissue sample was harvested from the anterior abdominal wall of the patient before resection and simultaneous reconstruction of the parasymphysis. ASCs were isolated and expanded ex vivo over the next 3 weeks. The cell surface marker expression profile of ASCs was similar to previously reported results and ASCs were analyzed for osteogenic differentiation potential in vitro. The expanded cells were seeded onto a scaffold consisting of β-TCP and BMP-2 and the cell viability was evaluated. The construct was implanted into the parasymphyseal defect.. Ten months after reconstruction, dental implants were inserted into the grafted site, allowing harvesting of bone cores. Histologic examination and in vitro analysis of cell viability and cell surface markers were performed and prosthodontic rehabilitation was completed.. ASCs in combination with β-TCP and BMP-2 offer a promising construct for the treatment of large, challenging mandibular defects without the need for ectopic bone formation and allowing rehabilitation with dental implants.

Topics: Adipose Tissue; Ameloblastoma; Bone Morphogenetic Protein 2; Bone Plates; Bone Regeneration; Bone Substitutes; Calcium Phosphates; Cell Culture Techniques; Cell Differentiation; Cell Survival; Dental Implants; Dental Prosthesis, Implant-Supported; Denture, Overlay; Denture, Partial; Follow-Up Studies; Humans; Male; Mandibular Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Osseointegration; Osteogenesis; Plastic Surgery Procedures; Recombinant Proteins; Stem Cells; Subcutaneous Fat, Abdominal; Surgical Mesh; Tissue Engineering; Tissue Scaffolds; Transforming Growth Factor beta

Microvascular osseous free tissue transfer is the standard of care for reconstructing significant mandibulectomy defects; however, this procedure can carry a significant rate of morbidity.. To describe the use of recombinant human bone morphogenetic protein 2 (rhBMP-2) as an option for segmental or near-complete rim mandibulectomy defects in a select group of patients, precluding the need for free tissue transfer.. A retrospective review was performed of 6 patients who had undergone repair of a mandible defect using rhBMP-2 with beta-tricalcium phosphate matrix or a cadaveric bone graft at a single tertiary care institution. The defects resulted from resection of benign neoplasms or from previous trauma. Reconstruction success was defined as no hardware problems, healing without infection, no need for further surgical procedures, and imaging evidence of healing and union without resorption. The median follow-up period was 37.5 months (range, 12-51 months).. Five of 6 patients underwent successful restoration of the mandibulectomy defect. One patient with a compromised immune system developed a significant postoperative wound infection requiring further reconstructive surgery.. The use of an rhBMP-2-based reconstructive approach is a feasible option for segmental or near-complete rim mandibulectomy defects in a select group of patients.. 4.

Topics: Ameloblastoma; Biocompatible Materials; Bone Morphogenetic Protein 2; Bone Transplantation; Calcium Phosphates; Female; Follow-Up Studies; Granuloma, Giant Cell; Guided Tissue Regeneration; Humans; Male; Mandibular Diseases; Mandibular Injuries; Mandibular Neoplasms; Mandibular Osteotomy; Mandibular Reconstruction; Middle Aged; Odontogenic Cysts; Recombinant Proteins; Reoperation; Retrospective Studies; Tissue Scaffolds; Transforming Growth Factor beta; Treatment Outcome

Ameloblastoma is a locally aggressive tumor most often found in posterior body and angle of the mandible. Although ameloblastoma has histological characteristics of benignity, they have a high percentage of local recurrence and possible malignant development if treated improperly.. This report presents a treatment of unusual mandibular sequelae after tumor resection using recombinant human bone morphogenetic protein-2 (rhBMP-2) associated with hydroxyapatite (HA) and calcium triphosphate (TCP).. Seven months after surgery, the patient was asymptomatic, with stable occlusion and class I, without signs of infection or rejection, and bone repair with rigidity compatible to an immature bone structure was observed. Reconstruction of large mandibular bone defect with a combination of rhBMP-2 and HA/TCP achieving a satisfactory result with less invasive and minimum morbidity has been demonstrated.

Topics: Adult; Ameloblastoma; Biocompatible Materials; Bone Morphogenetic Protein 2; Bone Plates; Bone Substitutes; Bone Transplantation; Calcium Phosphates; Collagen; Cutaneous Fistula; Device Removal; Drug Carriers; Durapatite; Equipment Failure; Female; Follow-Up Studies; Humans; Mandibular Neoplasms; Oral Fistula; Plastic Surgery Procedures; Recombinant Proteins; Surgical Mesh; Surgical Wound Dehiscence; Surgical Wound Infection; Transforming Growth Factor beta

The limitations and morbidity associated with autogenous bone grafting have driven the search for predictable bone substitutes and bioimplants. A novel method of reconstruction was tested in this case series.. Ten patients with major mandibular defects following resection of biopsy-proven ameloblastoma lesions or osteomyelitis of the mandibular body or ramus were included in this study. The resection defects were spanned with rigid reconstruction plates to hold the remaining mandibular segments in the correct position. The defects were filled with a bioimplant containing bone morphogenetic protein-7 (BMP-7) in a demineralized bone matrix (DBM) suspended in a reverse-phase medium to effect sustained BMP delivery.. The postoperative course for all 10 patients was uneventful. Radiographic evidence of mandibular bone formation was found in all cases. At the end of 1 year, functional and esthetic reconstruction of the mandible was complete.. Bioimplants containing BMP-7 in DBM suspended in a reverse phase medium were successful in restoring major mandibular defects in nonirradiated beds in this series of 10 patients.

Topics: Absorbable Implants; Adolescent; Adult; Aged; Ameloblastoma; Bone Matrix; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Bone Plates; Bone Regeneration; Bone Substitutes; Female; Humans; Male; Mandible; Mandibular Neoplasms; Middle Aged; Oral Surgical Procedures; Plastic Surgery Procedures; Transforming Growth Factor beta

To further clarify the roles of regulators of embryonic development, bone morphogenetic protein (BMPs) and their associated molecules, in oncogenesis and cytodifferentiation of odontogenic tumors, the expression of these regulator molecules were analyzed in epithelial odontogenic tumors as well as in tooth germs.. Tooth germs, ameloblastomas, adenomatoid odontogenic tumors, and malignant ameloblastomas were examined by RT-PCR and immunohistochemistry for detection of BMP-2, -4, -7, BMP receptors I and II (BMPR-I, BMPR-II), core-binding factor alpha1 (CBFA1), and osterix.. mRNA expression of BMPs, BMPRs, CBFA1, and osterix was detected in all odontogenic tissues. Immunohistochemical reactivity for BMPs, BMPRs, and CBFA1 was detected in both epithelial and mesenchymal cells of tooth germs and epithelial odontogenic tumors. BMPs and BMPRs were evidently expressed in odontogenic epithelial cells in tooth germs and epithelial odontogenic tumors. Acanthomatous ameloblastomas showed increased BMP-7 reactivity in keratinizing cells. Nuclear CBFA1 expression was detected scatteredly in odontogenic epithelial cells in normal and neoplastic odontogenic tissues, as well as in some mesenchymal cells in tooth germs and in some stromal cells in epithelial odontogenic tumors. Ameloblastic carcinomas showed low reactivity for BMPs, BMPRs, and CBFA1.. BMPs and their associated molecules might play a role in cytodifferentiation of normal and neoplastic odontogenic epithelium via epithelial-mesenchymal interactions.

Topics: Ameloblastoma; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 4; Bone Morphogenetic Protein 7; Bone Morphogenetic Protein Receptors, Type I; Bone Morphogenetic Protein Receptors, Type II; Bone Morphogenetic Proteins; Cell Differentiation; Cell Nucleus; Cell Transformation, Neoplastic; Core Binding Factor Alpha 1 Subunit; Epithelial Cells; Epithelium; Humans; Immunohistochemistry; Mesoderm; Odontogenic Tumors; Reverse Transcriptase Polymerase Chain Reaction; Sp7 Transcription Factor; Stromal Cells; Tooth Germ; Transcription Factors; Transforming Growth Factor beta

The molecular and genetic characteristics of ameloblastoma are still poorly understood. We analyzed gene expression in fresh-frozen ameloblastomas and human fetal tooth germs, using a cDNA microarray. Thirty-four genes exhibited significant changes in expression levels in the ameloblastoma. Eleven genes were overexpressed more than three-fold, and 23 genes were underexpressed to below 0.4 of the control level. The oncogene FOS was the most overexpressed gene (from eight- to 14-fold), followed by tumor-necrosis-factor-receptor 1 (TNFRSF1A). Genes for sonic hedgehog (SHH), TNF-receptor-associated-factor 3 (TRAF3), rhoGTP-ase-activating protein 4 (ARHGAP4), deleted in colorectal carcinoma (DCC), cadherins 12 and 13 (CDH12 and 13), teratocarcinoma-derived growth-factor-1 (TDGF1), and transforming growth-factor-beta1 (TGFB1) were underexpressed in all tumors. In selected genes, a comparison between cDNA microarray and real-time RT-PCR confirmed similar relative gene expression changes. The gene expression profile identifies candidate genes that may be involved in the origination of ameloblastoma and several genes previously unidentified in relation to human tooth development.

Topics: Adolescent; Adult; Aged; Ameloblastoma; Antigens, CD; Cadherins; Embryonic Induction; Epidermal Growth Factor; Female; Gene Expression Profiling; Genes, fos; GPI-Linked Proteins; Growth Substances; GTPase-Activating Proteins; Hedgehog Proteins; Humans; Intercellular Signaling Peptides and Proteins; Least-Squares Analysis; Male; Membrane Glycoproteins; Middle Aged; Neoplasm Proteins; Odontogenesis; Oligonucleotide Array Sequence Analysis; Proteins; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Regression Analysis; Reverse Transcriptase Polymerase Chain Reaction; TNF Receptor-Associated Factor 3; Tooth Germ; Trans-Activators; Transforming Growth Factor beta; Transforming Growth Factor beta1; Zinc Fingers

Desmoplastic ameloblastoma (DA) is an unusual subtype of ameloblastoma histologically characterized by the pronounced collagenized stroma. In the present study, the immunolocalization of transforming growth factor beta (TGF-beta), one of the most potent local factors for modulating extracellular matrix formation, was observed in DA in order to study its participation in the stromal desmoplasia. Seven cases of DA, including a "hybrid" lesion, were studied together with ten cases of ordinary follicular and plexiform ameloblastomas as the control. In contrast to ordinary ameloblastomas, marked immunoexpression was observed in all DAs but one. In the "hybrid" lesion, TGF-beta was not expressed in the area of follicular ameloblastoma but in that of DA. These results show that TGF-beta produced by tumor cells of DA plays a part in the desmoplastic matrix formation.

Topics: Adolescent; Adult; Ameloblastoma; Collagen; Female; Humans; Immunohistochemistry; Jaw Neoplasms; Male; Middle Aged; Transforming Growth Factor beta