Role of collagenases in tumor cell invasion.
Role of collagenases in tumor cell invasion.
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DOI：
10.1007/bf00124213
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发表时间：
1982-01-01
期刊：
影响因子：
--
通讯作者：
Garbisa, S
中科院分区：
文献类型：
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作者：
Liotta, L A;Thorgeirsson, U P;Garbisa, S
胶原酶是一个金属蛋白酶家族，可能在促进肿瘤细胞侵袭细胞外基质中发挥作用。在转移过程的多个阶段，肿瘤细胞穿过两种类型的细胞外基质：基底膜和间质基质。基质是胶原蛋白、蛋白多糖、弹性蛋白和糖蛋白的致密网络。通常，基质不包含足够大的开放空间以供细胞移动。因此，许多研究者推测，由肿瘤细胞或相关宿主细胞分泌的胶原溶解蛋白酶在肿瘤细胞侵袭期间分解细胞外基质。大量的动物和人类肿瘤已经显示出比相应的良性组织含有更高水平的胶原酶。已经鉴定了降解特定类型胶原的单独的胶原分解金属蛋白酶。在一系列转移性小鼠肿瘤细胞中，基底膜胶原溶解蛋白酶显示升高。使用胶原酶特异性抗体的免疫学研究已经证明，在体内，肿瘤细胞可以产生胶原酶。因此，在肿瘤细胞的培养系中鉴定胶原酶不是体外培养的人工产物。在某些情况下，肿瘤细胞可以诱导宿主细胞产生胶原酶。迄今为止，胶原酶实际上在侵袭中起作用的最佳证据来自于天然胶原酶抑制剂在体外阻断肿瘤细胞侵袭细胞外基质的实验。
Collagenases are a family of metalloproteinases which may play a role in facilitating tumor cell invasion of the extracellular matrix. Tumor cells traverse two types of extracellular matrix: basement membranes and interstitial stroma, at multiple stages of the metastatic process. The matrix is a dense meshwork of collagen, proteoglycans, elastin and glycoproteins. Normally the matrix does not contain open spaces large enough for cell movement. Therefore numerous investigators have postulated that collagenolytic proteases, secreted by tumor cells or associated host cells, breakdown the extracellular matrix during tumor cell invasion. A large number of animal and human tumors have been shown to contain collagenase at a higher level than corresponding benign tissues. Separate collagenolytic metalloproteinases have been identified which degrade specific types of collagen. A basement membrane collagenolytic protease was shown to be elevated in a series of metastatic murine tumor cells. Immunologic studies using antibodies specific for collagenase have demonstrated that in vivo, tumor cells can produce collagenase. Therefore identification of collagenase in cultured lines of tumor cells is not an artifact of in vitro cultivation. In some cases, tumor cells may induce host cells to produce collagenase. The best evidence to date that collagenases actually play a role in invasion is derived from experiments in which natural collagenase inhibitors block tumor cell invasion of extracellular matrix in vitro.