[Effects of HGF on the production of matrix metalloproteinases by colonic cancer cells DHD/K12].

T Aparicio, S Kermorgant, M J Lewin, T Lehy
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Abstract

Matrix metalloproteinases (MMPs) and growth factors such as hepatocyte growth factor (HGF) are implicated in tumoral progression of several digestive cancers. The rat DHD/K12 colonic cancer cell line is very invasive in vivo. We showed by RT-PCR and western immunoblotting the presence of HGF receptor, c-Met, in DHD/K12 cells. Then, we detected by zymography and western blots the secretion of MMP-2 and MMP-9 in the conditioned medium of these cells. After 24 or 48 h of culture in medium supplemented with HGF, transforming growth factor-alpha (TGF-alpha) or sodium butyrate, MMP production by DHD/K12 cells was stimulated by HGF and TGF-alpha and inhibited by sodium butyrate. Knowing the capacity of MMPs to degrade the extracellular matrix and thus to favour tumoral invasion, results suggest that HGF is implicated in the aggressive behaviour of DHD/K12 cells since it increased MMPs secretion by these cells.

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[HGF对结肠癌细胞DHD/K12产生基质金属蛋白酶的影响]。
基质金属蛋白酶(MMPs)和生长因子如肝细胞生长因子(HGF)与几种消化道癌症的肿瘤进展有关。大鼠DHD/K12结肠癌细胞系在体内具有很强的侵袭性。我们通过RT-PCR和western免疫印迹法发现,HGF受体c-Met在DHD/K12细胞中存在。然后,我们用酶谱法和western blot检测这些细胞在条件培养基中MMP-2和MMP-9的分泌情况。在添加HGF、转化生长因子- α (tgf - α)或丁酸钠的培养基中培养24或48 h后,HGF和tgf - α刺激DHD/K12细胞产生MMP,丁酸钠抑制其产生。了解MMPs降解细胞外基质的能力,从而促进肿瘤侵袭,结果表明HGF与DHD/K12细胞的侵袭行为有关,因为它增加了这些细胞的MMPs分泌。
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