Nishimura K, Kitamura M, Takada S, Nonomura N, Tsujimura A, Matsumiya K, Miki T, Matsumoto K, Okuyama A
Department of Urology, Osaka University Medical School, Suita, Japan.
Int J Urol. 1998 May;5(3):276-81. doi: 10.1111/j.1442-2042.1998.tb00603.x.
The growth and progression of prostate cancer depends on the stromal-epithelial interaction which is under paracrine control. Hepatocyte growth factor (HGF), produced by mesenchymal cells, is a multifunctional growth factor stimulating the movement and growth of epithelial cells including cancer cells. We therefore assessed the relationship between the invasive potential of prostate cancer and HGF in vitro.
Three human prostate cancer cell lines were used including PC-3 and DU145 (androgen-independent), and LNCaP (androgen-dependent). We studied the expression of the HGF receptor c-met proto-oncogene (c-met) by Western blot analysis, and also determined the effects of HGF on cell scattering, and the mechanisms of invasion and proliferation, by microscopic observation, the matrigel invasion chamber assay, and the MTT assay.
c-met was detected in PC-3 and DU145 cells, but not in the LNCaP cells. There was increased cell motility in the scatter assay and an increased cell invasive potential in the matrigel invasion chamber assay by stimulation with HGF only with DU145 cells.
HGF plays an important role in the invasion and metastasis of the DU145 cell line through a paracrine mechanism mediated by the c-metreceptor. In the PC-3 cell line, the lack of downstream signal transduction after the c-met receptor is suggested.
前列腺癌的生长和进展取决于旁分泌控制下的基质 - 上皮相互作用。间充质细胞产生的肝细胞生长因子(HGF)是一种多功能生长因子,可刺激包括癌细胞在内的上皮细胞的移动和生长。因此,我们在体外评估了前列腺癌的侵袭潜能与HGF之间的关系。
使用了三种人前列腺癌细胞系,包括PC - 3和DU145(雄激素非依赖性)以及LNCaP(雄激素依赖性)。我们通过蛋白质印迹分析研究了HGF受体c - met原癌基因(c - met)的表达,并通过显微镜观察、基质胶侵袭小室试验和MTT试验确定了HGF对细胞散射、侵袭和增殖机制的影响。
在PC - 3和DU145细胞中检测到c - met,但在LNCaP细胞中未检测到。仅用HGF刺激时,在散射试验中DU145细胞的细胞运动性增加,在基质胶侵袭小室试验中细胞侵袭潜能增加。
HGF通过c - met受体介导的旁分泌机制在DU145细胞系的侵袭和转移中起重要作用。在PC - 3细胞系中,提示c - met受体后缺乏下游信号转导。