Yi S, Chen J R, Viallet J, Schwall R H, Nakamura T, Tsao M S
Department of Pathology, Montreal General Hospital/Research Institute and McGill University, Montreal, Quebec, Canada.
Br J Cancer. 1998 Jun;77(12):2162-70. doi: 10.1038/bjc.1998.361.
We have studied the mitogenic, motogenic and morphogenic effects of hepatocyte growth factor (HGF), also known as scatter factor (SF), on 15 non-small-cell lung carcinoma (NSCLC) cell lines that have had their ras genotype determined. HGF/SF stimulated proliferation in only three cell lines and exerted no mitogenic activity on six lines. The growth of the remaining six lines was inhibited. The mitogenic effects were not related to the ras genotype of these cell lines, but the inhibitory effect was more commonly observed in cell lines with relatively high levels of Met/HGF receptor (HGFR) expression. HGF/SF induced or enhanced both scatter activity on monolayer culture and single-cell invasion in collagen gels in approximately half of these cell lines. Although the ras genotype of tumour cells did not influence the HGF/SF-induced motogenic activity, cell lines with the mutant ras genotype more commonly demonstrated a spontaneous motogenic activity than those with the wild-type ras genotype. When tumour cells were grown in collagen gels, HGF/SF induced irregular branching extensions of cell aggregates formed by five out of eight adenocarcinoma cell lines, but significant lumen morphogenesis was distinctly absent. The presence of autocrine HGF/SF loop in these tumour cell lines did not influence their spontaneous or HGF/SF-induced mitogenic, motogenic or morphogenic activities. Overall, our data suggest that stimulation of cell motility, rather than proliferation or differentiation, is the predominant paracrine effect of HGF/SF on NSCLC cells in vitro.
我们研究了肝细胞生长因子（HGF），也称为分散因子（SF），对15种已确定ras基因型的非小细胞肺癌（NSCLC）细胞系的促有丝分裂、促运动和形态发生作用。HGF/SF仅刺激了三种细胞系的增殖，而对六种细胞系没有促有丝分裂活性。其余六种细胞系的生长受到抑制。促有丝分裂作用与这些细胞系的ras基因型无关，但在Met/HGF受体（HGFR）表达水平相对较高的细胞系中更常观察到抑制作用。HGF/SF在大约一半的这些细胞系中诱导或增强了单层培养中的分散活性以及胶原凝胶中的单细胞侵袭。尽管肿瘤细胞的ras基因型不影响HGF/SF诱导的促运动活性，但具有突变ras基因型的细胞系比具有野生型ras基因型的细胞系更常表现出自发性促运动活性。当肿瘤细胞在胶原凝胶中生长时，HGF/SF诱导了八种腺癌细胞系中的五种形成的细胞聚集体出现不规则分支延伸，但明显没有显著的管腔形态发生。这些肿瘤细胞系中自分泌HGF/SF环的存在不影响它们的自发或HGF/SF诱导的促有丝分裂、促运动或形态发生活性。总体而言，我们的数据表明，在体外，刺激细胞运动而非增殖或分化是HGF/SF对NSCLC细胞的主要旁分泌作用。
