Nishimura K, Kitamura M, Miura H, Nonomura N, Takada S, Takahara S, Matsumoto K, Nakamura T, Matsumiya K
Department of Urology, Osaka University Medical School, Suita, Japan.
Prostate. 1999 Nov 1;41(3):145-53. doi: 10.1002/(sici)1097-0045(19991101)41:3<145::aid-pros1>3.0.co;2-r.
In prostate cancer, several growth factors derived from stromal cells regulate tumor cell growth. Hepatocyte growth factor (HGF) possesses biological activities that promote cancer proliferation and invasion through tumor-stromal interaction. We examined how prostate stromal cell-derived HGF affects invasion of prostate cancer cells through this interaction.
The effects of HGF, various growth factors (transforming growth factor (TGF)-alpha, TGF-beta1, basic fibroblast growth factor, keratinocyte growth factor, and platelet-derived growth factor), and conditioned medium (CM) from prostate stromal cells (PrSC) on prostate cancer cells (LNCaP, PC-3, and DU145) were determined by collagen gel invasion assay. DU145 cells and PrSC were cocultured for Matrigel invasion chamber assay. Induction activity of CM from cancer cells to stimulate HGF production by PrSC was studied by the ELISA method and Western blotting.
LNCaP and PC-3 cells did not respond to any of the factors examined. Invasion of DU145 cells into the collagen gel matrix was induced by HGF and TGF-beta1, but not by any of the other factors tested. When DU145 cells were cultured in CM from PrSC or cocultured with PrSC, the cells acquired invasive potential, and this invasion was inhibited by an antibody against HGF, but not against TGF-beta1. Native-type HGF production in PrSC was enhanced by some unknown inducer(s) produced by cancer cells.
PrSC-derived HGF enhanced invasive activity of the prostate cancer cell line DU145 through tumor-stromal interaction, wherein DU145 cells secreted some HGF-inducer(s) for PrSC.
在前列腺癌中，几种源自基质细胞的生长因子调节肿瘤细胞的生长。肝细胞生长因子（HGF）具有通过肿瘤-基质相互作用促进癌症增殖和侵袭的生物学活性。我们研究了前列腺基质细胞衍生的HGF如何通过这种相互作用影响前列腺癌细胞的侵袭。
通过胶原凝胶侵袭试验确定HGF、各种生长因子（转化生长因子（TGF）-α、TGF-β1、碱性成纤维细胞生长因子、角质形成细胞生长因子和血小板衍生生长因子）以及前列腺基质细胞（PrSC）的条件培养基（CM）对前列腺癌细胞（LNCaP、PC-3和DU145）的影响。将DU145细胞和PrSC共培养用于基质胶侵袭小室试验。通过ELISA法和蛋白质印迹法研究癌细胞CM刺激PrSC产生HGF的诱导活性。
LNCaP和PC-3细胞对所检测的任何因子均无反应。HGF和TGF-β1可诱导DU145细胞侵入胶原凝胶基质，但其他所检测因子均无此作用。当DU145细胞在PrSC的CM中培养或与PrSC共培养时，细胞获得侵袭潜能，且这种侵袭被抗HGF抗体抑制，但不被抗TGF-β1抗体抑制。癌细胞产生的一些未知诱导剂可增强PrSC中天然型HGF的产生。
PrSC衍生的HGF通过肿瘤-基质相互作用增强前列腺癌细胞系DU145的侵袭活性，其中DU145细胞分泌一些PrSC的HGF诱导剂。
