Kramer M D, Reinartz J, Brunner G, Schirrmacher V
Institute for Immunology and Serology, University of Heidelberg, Germany.
Invasion Metastasis. 1994;14(1-6):210-22.
Invasive tumor growth or severe inflammation is accompanied by the extravasation of fibrinogen from leaky or damaged blood vessels and the formation of a fibrin clot. The clot provides a matrix for the inward migration ('invasion,' 'infiltration') of tumor cells as well as inflammatory cells. The factors that govern the cell/fibrin interaction are not known. We have explored in vitro the possible role of the cell-surface-associated pathway of plasminogen activation in the adhesion of keratinocytes to fibrin and in the invasion of melanoma cells into fibrin gels. Our experiments provided evidence that generation of plasmin at the cell surface destabilizes the adhesive interaction between keratinocytes and fibrin, most likely by cleaving fibrin into fibrinopeptides and destroying its adhesive capacity. Moreover, we found that plasmin generated at the melanoma cell surface promotes the inward migration of these cells into three-dimensional fibrin matrices. In conclusion, the generation of plasmin at the cellular surface may be an important factor in pericellular proteolysis and the dynamic interaction between cells and fibrin-containing pericellular matrix under conditions of tumor invasion and inflammation.
侵袭性肿瘤生长或严重炎症伴随着纤维蛋白原从渗漏或受损血管中渗出并形成纤维蛋白凝块。该凝块为肿瘤细胞以及炎症细胞的向内迁移（“侵袭”“浸润”）提供了一个基质。目前尚不清楚调控细胞/纤维蛋白相互作用的因素。我们在体外研究了纤溶酶原激活的细胞表面相关途径在角质形成细胞与纤维蛋白黏附以及黑色素瘤细胞侵入纤维蛋白凝胶过程中可能发挥的作用。我们的实验提供了证据表明，细胞表面纤溶酶的产生破坏了角质形成细胞与纤维蛋白之间的黏附相互作用，很可能是通过将纤维蛋白裂解为纤维蛋白肽并破坏其黏附能力。此外，我们发现黑色素瘤细胞表面产生的纤溶酶促进了这些细胞向三维纤维蛋白基质的向内迁移。总之，细胞表面纤溶酶的产生可能是肿瘤侵袭和炎症条件下细胞周围蛋白水解以及细胞与含纤维蛋白的细胞周围基质之间动态相互作用的一个重要因素。
