Tenascin-C upregulates matrix metalloproteinase-9 in breast cancer cells:: Direct and synergistic effects with transforming growth factor β1
Tenascin-C upregulates matrix metalloproteinase-9 in breast cancer cells:: Direct and synergistic effects with transforming growth factor β1
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DOI：
10.1002/ijc.11037
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发表时间：
2003-05-20
影响因子：
6.4
通讯作者：
Yoshida, T
中科院分区：
文献类型：
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作者：
Kalembeyi, I;Inada, H;Yoshida, T
腱生蛋白-C（TN-C）和基质金属蛋白酶（MMPs）在癌组织中高度表达，并可能在癌症进展过程中促进细胞迁移。TN-C和MMPs通常共同定位于病理条件下活跃的组织重塑区域，表明相互调节。为了研究TN-C是否调节癌细胞中MMPs的表达，我们首先将来自TN-C缺陷小鼠的乳腺癌细胞暴露于TN-C并检测MMPs的表达。然后将TN-C与纤维连接蛋白（FN）、层粘连蛋白（LN）、碱性成纤维细胞生长因子（b-FGF）和转化生长因子-β 1（TGF-β 1）进行比较。终点RT-PCR、定量实时RT-PCR和明胶酶谱分析结果表明，TN-C强烈且呈剂量依赖性地上调小鼠乳腺癌细胞中MMP-9的表达。TN-C对MMP-2、MMP-3和MMP-13的诱导作用较弱。FN和LN对MMP-9的诱导作用低于TN-C。b-FGF对MMP-9表达无影响。TGF-β 1以剂量依赖性方式诱导MMP-9表达，并且这种诱导作用通过添加TN-C显著增强。TN-C和TGF-β 1也上调人乳腺癌细胞系MDA-MB-231中MMP-9的表达。用特异性抗TGF-β 1抗体中和显示MMP-9表达降低，表明TGF-β通过直接自分泌机制控制基线MMP-9表达。在中和TGF-β的情况下，添加TN-C仍然上调MMP-9。相反，内源性TN-C的中和（在TN-C阳性乳腺癌细胞系中）下调TGF-β诱导的MMP-9表达。因此，TN-C直接诱导MMP-9表达，并与TGF-β协同诱导MMP-9表达。这些发现揭示了TN-C在乳腺癌进展中的新作用。(C)2003 Wiley-Liss，Inc.
Tenascin-C (TN-C) and matrix metalloproteinases (MMPs) are highly expressed in cancer tissues and probably promote cell migration during cancer progression. TN-C and MMPs are often co-localized in areas of active tissue remodeling in pathologic conditions, suggesting reciprocal regulation. To investigate whether TN-C regulates MMPs expression in cancer cells, we first exposed mammary cancer cells derived from TN-C-deficient mice to TN-C and examined MMPs expression. TN-C was then compared with fibronectin (FN), laminin (LN), basic fibroblast growth factor (b-FGF) and transforming growth factor-betal (TGF-beta1). Results of endpoint RT-PCR, quantitative real-time RT-PCR and gelatin zymography demonstrated that TN-C, strongly and dose dependently, upregulates MMP-9 expression in murine mammary cancer cells. TN-C weakly induced MMP-2, MMP-3 and MMP-13. FN and LN induced MMP-9 to lesser extents compared with TN-C. b-FGF had no effect on MMP-9 expression. TGF-beta1 induced MMP-9 expression in a dose-dependent manner, and this induction was significantly enhanced by addition of TN-C. TN-C and TGF-beta1 also upregulated MMP-9 expression in the human breast cancer cell line MDA-MB-231. Neutralization with specific anti-TGF-beta1 antibody showed decreased expression of MMP-9, indicating that TGF-beta controls the baseline MMP-9 expression by a direct autocrine mechanism. Under neutralization of TGF-beta, addition of TN-C still upregulated MMP-9. Conversely, neutralization of endogenous TN-C (in a TN-C-positive mammary cancer cell line) downregulated TGF-beta-induced MMP-9 expression. Thus, TN-C induces MMP-9 expression directly and by collaboration with TGF-beta. These findings reveal a novel role of TN-C in breast cancer progression. (C) 2003 Wiley-Liss, Inc.