Mackay A R, Corbitt R H, Hartzler J L, Thorgeirsson U P
Division of Cancer Etiology, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Cancer Res. 1990 Sep 15;50(18):5997-6001.
Current hypotheses suggest that both the plasmin system and metalloproteinases are involved in tumor invasion of basement membrane. In this study, we demonstrate that plasmin can directly degrade native and denatured type IV collagen in solution as well as in tissue sections. Tumor cell lines secreted plasminogen activators into culture supernatants that activated exogenous plasminogen to degrade type IV collagen in zymograms and to remove collagen IV immunoreactivity from tissue sections. Inhibition of metalloproteinase activity in culture supernatants by EDTA did not interfere with plasminogen-mediated type IV collagen degradation. We propose that tumor cells possess a mechanism for the degradation of basement membrane type IV collagen, independent of metalloproteinases but dependent on plasminogen conversion to plasmin.
目前的假说认为，纤溶酶系统和金属蛋白酶都参与肿瘤对基底膜的侵袭。在本研究中，我们证明纤溶酶能够直接降解溶液以及组织切片中的天然和变性IV型胶原。肿瘤细胞系将纤溶酶原激活剂分泌到培养上清液中，这些激活剂可激活外源性纤溶酶原，在酶谱中降解IV型胶原，并从组织切片中去除IV型胶原免疫反应性。用EDTA抑制培养上清液中的金属蛋白酶活性并不干扰纤溶酶原介导的IV型胶原降解。我们提出，肿瘤细胞拥有一种降解基底膜IV型胶原的机制，该机制不依赖于金属蛋白酶，而是依赖于纤溶酶原转化为纤溶酶。
