Role of FGF-2 in interaction of oral squamous cell carcinoma cells and fibroblasts in an in vitro invasion system

Abstract

Stromal fibrosis occurs as a host reaction to invasion and proliferation of cancer cells, and cancer cells are activated through their interaction with proliferating fibroblasts. However, the detailed mechanism remains to be clarified. In this study, we investigated the influence of FGF-2, which is excessively expressed in cancer cells at the invasive front, on the proliferation of fibroblasts and invasion and proliferation of cancer cells in vitro. The culture supernatant of three cell strains of human oral squamous cell carcinoma (OSC-20: type 3; OSC-19: type 4C; and HOC313: type 4D), among which the mode of cancer invasion differed, promoted proliferation of human normal gingival fibroblasts (HGF-1) . In particular, the culture supernatant of HOC313 cells markedly promoted proliferation of HGF-1 cells, and FGF-2 expression in the supernatant was more marked than in the culture supernatant of OSC-20 and OSC-19 cells. Furthermore, Recombinant Human FGF-2 (50ng/ml) promoted not only proliferation of HGF-1 cells but also invasion and proliferation of each cancer cell, and the levels of OSC-19 and HOC313 cells were significantly higher than the control values (p<0.05) . In an in vitro invasion model, addition of an FGF-2-neutralizing antibody (2μg/ml) inhibited invasion of OSC-20 and OSC-19 cells. These results suggest that highly invasive squamous cell carcinoma cells produce FGF-2 and promote invasion and proliferation activity of cancer cells via autocrine, whereas it is involved in the proliferation of fibroblasts via paracrine.