ENHANCING EFFECTS OF EPIDERMAL GROWTH FACTOR ON HUMAN ORAL SQUAMOUS CELL CARCINOMA INVASION AND METASTASIS.

1)表皮生长因子旁分泌方式对口腔鳞癌侵袭能力的影响为明确表皮生长因子对口腔鳞癌侵袭能力的影响，对5种口腔鳞状细胞癌细胞系进行了体外侵袭实验。EGF以剂量依赖的方式增强所有细胞系的随机运动能力，并使相同细胞产生的尿激酶型纤溶酶原激活剂和基质金属蛋白酶-9增加。这些结果强烈提示EGF可能促进口腔鳞癌的侵袭和转移。(肿瘤生物学，17：168-175,1996)2)EGF在自分泌MANNER细胞系中的作用。在这些细胞中，肿瘤细胞产生的EGF可以通过EGF受体本身刺激其随机运动。(3)表皮生长因子敏感克隆的建立为了揭示信号通路，我们建立了对表皮生长因子最敏感的克隆S-1克隆细胞和对表皮生长因子最不敏感的克隆I-1克隆细胞。4)EGF诱导运动的信号转导分析。当EGF与EGF受体结合时，首先发生酪氨酸磷酸化，然后通过激活由erbB同源二聚体产生的PLCR和/或由erbB3异源二聚体产生的PI3-激酶来激活PKC。(JJCR会议录，第54届年会，第458页)

1) Effect of EGF in paracrine mannerIn order to clear the effects of Epidermal Growth Factor (EGF) on the invasion abilities of human oral squamous cell carcinoma, five cell lines were studied. EGF enhanced the random motility of all cell lines in a dose-dependent fashion and exposure to EGF let to an increased production of urokinase type plasminogen activator and matrix metalloproteniase-9 by the same cells. These results strongly suggest the EGF may promote the invasion and metastasis of human oral squamous cell carcinomas. (Tumor Biology, 17 : 168-175,1996.)2) EFFECT OF EGF IN AUTOCRINE MANNERCell lines, which produced EGF,was found out in these cell lines. In these cells, EGF produced by tumor cells can stimulate the random motility itself through the EGF receptor. (Oncologia 27 : 455-457,1994)3) ESTABLISHMENT OF EGF SENSITIVE CLONETo reveal the signal pathway, we established s-1 clone cells, which was most sensitive clone against the EGF stimulation and also we established i-1 clone cells, which was most insensitive clone. Comparison of these clone cells may lead the mechanisms of signal transduction of EGF-induced motility in near future.4) ANALYSIS OF SIGNAL TRANSDUCTION OF EGF-INDUCED MOTILITY.When EGF bind to the EGF receptor, tyrosine phosphorelation is firstly occurred and subsequently PKC is activated through the activation of PLCr arising from erbB homodimer and/or activation of PI3-kinase arising from erbB3 heterodimer. (Proceeding of JJCR,54th Annual Meeting, P458)