Proteolysis of extracellular matrix by invadopodia facilitates human breast cancer cell invasion and is mediated by matrix metalloproteinases

Proteolysis of extracellular matrix by invadopodia facilitates human breast cancer cell invasion and is mediated by matrix metalloproteinases
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DOI:
10.1023/a:1006538200886
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发表时间:
1998-08-01
影响因子:
4
通讯作者:
Chu, WS
Chu, WS
中科院分区:
医学3区
文献类型:
--
作者:
Kelly, T;Yan, Y;Chu, WS

文献摘要

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乳腺癌细胞系的侵袭行为各不相同,一种高度侵袭性的细胞系(MDA-MB-231)通过侵袭伪足蛋白水解降解细胞外基质(Thompson等,1992,J Cell Physiol,150,534-44; Chen等,1994,Breast Cancer Res Treat,31,217-26),细胞外基质的侵入伪足蛋白水解被认为是侵入所必需的;然而,这还没有被直接证明,为了获得这样的证据,正常(HBL-100)和恶性(MCF-7,MDA-MB-231)乳腺细胞的侵袭性蛋白水解细胞外基质和侵袭行为进行了评估。我们报告了固定化纤维连接蛋白的侵袭性蛋白水解与细胞侵入I型胶原凝胶呈正相关,此外,用金属蛋白酶抑制剂巴马司他(BB-94)降低侵袭伪足的蛋白水解活性也降低了侵袭,表明乳腺癌细胞侵袭依赖于蛋白水解活性的侵袭伪足。
Breast cancer cell lines vary in invasive behavior and one highly invasive cell line (MDA-MB-231) proteolytically degrades extracellular matrix with invadopodia (Thompson et al, 1992, J Cell Physiol, 150, 534-44; Chen et al, 1994, Breast Cancer Res Treat, 31, 217-26), Invadopodial proteolysis of extracellular matrix is thought to be necessary for invasion; however, this has not been demonstrated directly, To obtain such evidence, normal (HBL-100) and malignant (MCF-7, MDA-MB-231) breast cells were evaluated for invadopodial proteolysis of extracellular matrix and invasive behavior, We report that invadopodial proteolysis of immobilized fibronectin, is positively correlated with invasion of cells into type I collagen gels, Moreover, reducing the proteolytic activity of invadopodia with the metalloproteinase inhibitor, batimastat (BB-94), also decreases invasion indicating that breast cancer cell invasion is dependent upon proteolytically active invadopodia.