Autocrine Growth Factor Produced by Oral Cancer

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We have established serum-free culture system for normal epithelial cell and cancer cells from oral mucosa and salivary gland. Normal epithelial cells absolutely required EGF or FGF for the growth in serum-free culture and oral cancer cells exhibited lowered or lost reguirement of EGF and FGF for growth compare to normal cells. EGF stimulated growth of Salivary gland-derived Adenocarcinoma Cells (SAC) but inhibited that of Squamous Cell Carcinoma cells (SCC). FGF stimulated growth of SAC but did not show any significant effects on SCC cell. But we could not find any significant differences in the expression of EGF and FGF receptors of these cells. Thus, it was speculated EGF and/or FGF receptors expressed in SCC cells were functionally different from that of normal cells.At the second years, we have found autocrine growth factor activities in the medium conditioned by SAC. The activites were resulted from EGFーlike and FGF-like activities. Furthermore, we have found that SCC cells produced membrane-bound transforming growth factor-alpha as an autocrine growth factor. Thus we have generated monoclonal antibodies against EGF receptor (EGFr) designated 12-93. As the result of immunohistchemical examination, EGFr was expressed in basal cells and ductal epithelial cells in normal oral mucosa and salivary gland, respectively. On the other hand, SCC and SAC cells exhibi ting ductal formation expressed EGFr. Furthermore, we have found 12-93 inhibited growth of SCC and SAC in serum-free culture. In addition to these findings, it also inhibited the formation of tumors which transplanted in athymic mice. These results obtained are thus for encouraging and indicate that mono clonal antibodies to autocrine growth factors and/or its receptor eventually to be viable therapeutic agents to treat oral cancer.