Role of Heparanase in the Release of Heparan Sulphate Binding Growth Factors in Odontogenic Tumors

Abstract

Immunolocalization of heparan sulphate(HS) and heparanase was evaluated in benign and malignant odontogenic tumors in order to know whether these molecules have potential roles in odontogenic tumorigenesis. Archival formalin-fixed, paraffin-embedded tissues of 6 human tooth germs, 7 adenomatoid odontogenic tumors, 10 ameloblastic fibromas, 20 ameloblastomas and 4 ameloblastic carcinomas were subjected to immunohistochemical staining using antibodies to HS, heparanase and BMP-4. HS was ubiquitously localized in tooth germ but heparanase and BMP-4 were observed in limited areas only. In benign epithelial tumors such as ameloblastoma and adenomatoid odontogenic tumor, these molecules were localized in neoplastic epithelium but in ameloblastic fibroma, positive reactions were observed in both epithelial and mesenchymal cells. Stromal localization of HS and BMP-4 accompanied by intense immunoexpression of epithelial heparanase was observed in ameloblastic carcinoma, and this may represent the malignant progression of ameloblastoma to ameloblastic carcinoma. Stronger intensity and more diffuse localization of heparanase in odontogenic tumors compare to that of human tooth germ was the most significant finding. Taken together, the results inferred that heparanase may be responsible for the growth and progression of odontogenic tumors by modulating the availability and function of HS binding growth factors and the derangement in immunoexpression and localization of HS and heparanase molecules may have important roles in progression of malignant odontogenic tumors.