MMP-2 release and activation in ovarian carcinoma: the role of fibroblasts
MMP-2 release and activation in ovarian carcinoma: the role of fibroblasts
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DOI：
10.1038/sj.bjc.6690357
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发表时间：
1999-05-01
影响因子：
8.8
通讯作者：
Balkwill, FR
中科院分区：
文献类型：
--
作者：
Boyd, RS;Balkwill, FR
基质金属蛋白酶 MMP-2 在上皮癌中上调，其 mRNA 定位于基质成纤维细胞。在本文中，我们表明卵巢癌细胞与成纤维细胞的共培养导致 proMMP-2 和 TIMP-2 向培养基中的释放增强。细胞间相互作用是这种反应的主要因素，癌细胞刺激成纤维细胞释放 proMMP-2，但反之则不然。胶原蛋白 1 以剂量依赖性方式诱导肿瘤来源的成纤维细胞（而非正常的成纤维细胞）激活 proMMP-2。 β(1) 整合素抗体还诱导肿瘤来源的成纤维细胞激活 proMMP-2。激活过程涉及膜结合金属蛋白酶对 proMMP-2 的加工。我们认为，在卵巢肿瘤微环境中，肿瘤细胞和成纤维细胞之间的相互作用可能会增强成纤维细胞 proMMP-2 和 TIMP-2 的产生。 I 型胶原蛋白也存在于卵巢肿瘤中，即使在 TIMP-2 存在的情况下，也会诱导这些成纤维细胞激活 proMMP-2。这种活性MMP-2可以与肿瘤细胞和成纤维细胞的细胞表面结合，并用于组织重塑和侵袭过程。
The matrix metalloproteinase MMP-2 is up-regulated in epithelial cancers and its mRNA localizes to stromal fibroblasts. In this paper we show that co-culture of ovarian carcinoma cells with fibroblasts resulted in an enhanced release of proMMP-2 and TIMP-2 into the culture medium. Cell-cell interaction was a major factor in this response and carcinoma cells stimulated proMMP-2 release from fibroblasts but not vice versa. Collagen 1, in a dose-dependent fashion, induced activation of proMMP-2 by tumour-derived, but not normal, fibroblasts. Antibody to beta(1) integrin also induced proMMP-2 activation by tumour-derived fibroblasts. The activation involved the processing of proMMP-2 by a membrane-bound metalloproteinase. We propose that, in the ovarian tumour microenvironment, interaction between tumour cells and fibroblasts may enhance fibroblast production of the proMMP-2 and TIMP-2. Collagen I, also present in the ovarian tumours, then induces these fibroblasts to activate proMMP-2 even in the presence of TIMP-2. This active MMP-2 can associate with the cell surface of tumour cells and fibroblasts and is used in the processes of tissue remodelling and invasion.