Immunohistochemical detection of hepatocyte growth factor, transforming growth factor‐β and their receptors in epithelial odontogenic tumors

Abstract

Immunohistochemical localization of HGF, TGF-beta and their receptors in tooth germs and epithelial odontogenic tumors supports the hypothesis that HGF and TGF-beta act on epithelial cells via paracrine and autocrine mechanisms. Altered expression of the agents in these epithelial odontogenic tumors, especially subtypes of ameloblastomas, AOTs and COCs, suggests that HGF and TGF-beta signaling might affect differentiation of neoplastic odontogenic epithelial cells. Activated HGF/c-Met pathway and reduced TGF-beta signaling in CCOTs and ameloblastic carcinomas may be associated with the malignant potential of these epithelial odontogenic tumors.

Comparação da imunoexpressão de VEGF, TGF-β e MMP-9 em ameloblastoma e tumor odontogênico adenomatóide

“…This finding may be closely related to the angiogenesis and invasive biological behavior of ameloblastomas, corroborating the studies of Chen et al [1] and Kumamoto et al [13] who have already suggested that VEGF is an important mediator of angiogenesis in these epithelial odontogenic tumors. Its up-regulation might be associated with malignant neoplastic changes of odontogenic epithelial cells.…”

“…These processes play a key role in repairing and remodeling bone during development and, in odontogenic tumors, they promote bone resorption [13]. Numerous observations have shown that VEGF is generated from a variety of cells inside or in the close vicinity of blood vessels under many physiological or pathological conditions and it acts as a major player in the initial step of angiogenesis [13].…”

Molecular alterations in the development and progression of odontogenic tumors

“…Recently, overexpression of the EGFR family members, Her-2 and Her-3, has been identified in keratocystic odontogenic tumors (26,67). TGF-β and its receptors are expressed in many types of odontogenic tumors, suggesting that they have an important role in cell differentiation and matrix formation via regulation or dysregulation of epithelial-mesenchymal interactions (24,66,(68)(69)(70). HGF and its receptor c-Met, essential for morphogenesis of tooth germs, are expressed in many types of odontogenic tumors, suggesting that they affect epithelialmesenchymal interactions not only in developing teeth but also in neoplastic odontogenic tissues (24,70).…”

“…TGF-β and its receptors are expressed in many types of odontogenic tumors, suggesting that they have an important role in cell differentiation and matrix formation via regulation or dysregulation of epithelial-mesenchymal interactions (24,66,(68)(69)(70). HGF and its receptor c-Met, essential for morphogenesis of tooth germs, are expressed in many types of odontogenic tumors, suggesting that they affect epithelialmesenchymal interactions not only in developing teeth but also in neoplastic odontogenic tissues (24,70). Increased expression of HGF and c-Met in ameloblastic carcinomas and clear cell odontogenic carcinomas implies that HGF signaling might be associated with the malignant potential of epithelial odontogenic tumors (70).…”

“…HGF and its receptor c-Met, essential for morphogenesis of tooth germs, are expressed in many types of odontogenic tumors, suggesting that they affect epithelialmesenchymal interactions not only in developing teeth but also in neoplastic odontogenic tissues (24,70). Increased expression of HGF and c-Met in ameloblastic carcinomas and clear cell odontogenic carcinomas implies that HGF signaling might be associated with the malignant potential of epithelial odontogenic tumors (70). Expression of FGF-1, 2, and their type 2 and 3 receptors has been detected in various odontogenic tumors (71)(72).…”