Autocrine Growth Factor Produced by Oral Cancer

我们已经建立了一个用于正常表皮细胞和癌症细胞的无血清培养系统，用于正常表皮细胞和癌症细胞。正常表皮细胞在无血清培养和口腔癌细胞中的生长绝对需要的EGF或FGF对正常细胞的生长进行了抑制或丢失的限制，以促进正常细胞的生长。EGF stimulated growth of Salivary gland-derived Adenocarcinoma Cells （SAC） but inhibited that of Squamous Cell Carcinoma cells （SCC）。FGF对SAC细胞的刺激增长，但没有显示出对SCC细胞的任何显著影响。但我们无法在这些细胞的表达中发现EGF和FGF受体的任何显著差异。因此，它被指定为EGF和/或FGF受体在SCC细胞中的功能与正常细胞不同。在第二年，我们在SAC中发现了具有中等条件的自动生长因子活动。这些活动是从EGF-样和FGF-样活动中得到的。Furthermore，我们找到了一个SCC细胞生产的膜-绑定转化生长因子-alpha作为一个自动生长因子。因此，我们已经产生了一种针对EGF受体（EGFr）的单克隆抗体。作为免疫性化学试验的结果， EGFr被描述为在正常口腔霉菌和水生土壤中的碱性细胞和半导体外延细胞，对此表示赞赏。On the other hands， SCC and SAC cell exhibiting ductal formation expressed EGFr。Furthermore，我们在无血清文化中发现了12-93抑制的SCC和SAC增长。在对这些发现的补充中，它也抑制了在运动性老鼠中移植的肿瘤形成。这些结果是为了增强和指示单克隆抗体，以促进自动生长因子和/或其受体最终成为治疗口腔癌的有效治疗剂。

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.