Guirouilh J, Castroviejo M, Balabaud C, Desmouliere A, Rosenbaum J
Groupe de Recherches pour l'Etude du Foie, INSERM E 9917, 33076 Bordeaux cedex, France.
Int J Oncol. 2000 Oct;17(4):777-81. doi: 10.3892/ijo.17.4.777.
Hepatocellular carcinoma (HCC), the main type of primary liver cancer, is characterized by a high rate of intra-hepatic invasion. The stroma of HCC is infiltrated by myofibroblasts. We have previously shown that hepatocyte growth factor (HGF) secreted by human liver myofibroblasts greatly increased the in vitro invasiveness of 3 human HCC cell lines. In this study we show that the conditioned medium (CM) from the same HCC cell lines dose-dependently stimulates HGF secretion by myofibroblasts. This effect was post-transcriptional as no increase in HGF mRNA was observed. We show that the effect of CM is not due to IL-1, IL-6, IGF-1, bFGF or PDGF, previously shown to stimulate HGF synthesis in other models. Our data demonstrate that HCC cells increase HGF secretion by liver myofibroblasts in a paracrine way that could act to enhance invasion.
肝细胞癌(HCC)是原发性肝癌的主要类型,其特征是肝内侵袭率高。HCC的基质中有肌成纤维细胞浸润。我们之前已经表明,人肝脏肌成纤维细胞分泌的肝细胞生长因子(HGF)极大地增加了3种人HCC细胞系的体外侵袭性。在本研究中,我们发现来自相同HCC细胞系的条件培养基(CM)以剂量依赖的方式刺激肌成纤维细胞分泌HGF。这种作用是转录后水平的,因为未观察到HGF mRNA增加。我们表明,CM的作用不是由之前在其他模型中显示可刺激HGF合成的白细胞介素-1(IL-1)、白细胞介素-6(IL-6)、胰岛素样生长因子-1(IGF-1)、碱性成纤维细胞生长因子(bFGF)或血小板衍生生长因子(PDGF)引起的。我们的数据表明,HCC细胞以旁分泌方式增加肝脏肌成纤维细胞的HGF分泌,这可能起到增强侵袭的作用。