Mutual paracrine effects of oral squamous cell carcinoma cells and normal oral fibroblasts: Induction of fibroblast to myofibroblast transdifferentiation and modulation of tumor cell proliferation

Several tines of evidence demonstrated that the stroma surrounding the tumors plays an important rote in the growth and progression of several neoplasms, including oral squamous cell carcinomas (OSCC). We evaluated the presence of myofibroblasts in OSCC and determined whether their presence is associated with clinicopathological features of the tumors. We also investigated the mutual paracrine effects of tumor cells and myofibroblasts on fibroblast-myofibroblast transdifferentiation and tumor cell, proliferation. Immunohistochemical analysis showed the similar to 60% of the OSCCs contained myofibroblasts in the stroma of the tumor. Abundant presence of myofibroblasts significantly correlated with N stage, disease stage, regional recurrence, and proliferative potential. of the tumor cells. Using OSCC cell tines and primary oral, normal fibroblasts (ONF), we demonstrated that tumor cells induced transdifferentiation of ONFs to myofibroblasts via secretion of transforming growth factor-betal (TGF-beta 1). In turn, myofibroblasts secreted factors that stimulated OSCC cell proliferation, as revealed by measuring BrdU incorporation and Ki67 expression. The results of the study suggest that during tumor invasion OSCC-derived TGF beta 1 promote fibroblast-myofibroblast transdifferentiation, and that tumor cellular proliferation can be induced by factors released from myofibroblasts, which may favor tumor growth. (c) 2007 Etsevier Ltd. All rights reserved.