Wakabayashi H, Kawaguchi T
Department of Pathology II, Fukushima Medical College, Japan.
Invasion Metastasis. 1992;12(5-6):284-300.
The invasiveness of human gastric carcinoma cell lines (MKN45 and MKN28) in the subcutaneous tissue of nude mice and the degrading capacities of extracellular matrix (ECM) were studied. MKN45 cells were more invasive than were the MKN28 cells. Immunostaining revealed dense lamellar accumulation of fibronectin (FN) around the tumors. Along the front of the invasive MKN45 growth, however, the FN fibers were discontinuous and/or had completely vanished; the MKN28 tumor showed no FN fiber disconnection. ECM components other than FN never displayed such peritumoral massive accumulation. Cocultivation of human fibroblasts with MKN45 cells, more evidently than with MKN28 cells, revealed degradation of FN produced by fibroblasts in contact with each tumor. Both cell lines produced several FN-degrading enzymes in serum-free cultures. Proteases from the MKN45 medium were more active than were those of MKN28 in urokinase-type plasminogen activator (uPA) and metal-dependent serine proteinase-like proteases of 75 and 68 kDa in molecular weight (MW). Type I collagen-degrading 48-kDa protease was also detected from MKN45 medium but not from the MKN28 medium. MKN28 cells secreted other kinds of FN-degrading enzymes, estimated at approximate MWs of 29 and 100-150 kDa. We found no distinct differences in capacity to produce ECM components or ability to adhere to purified ECM components between these two cell lines. From these results we conclude that the stromal invasion of these cells into the subcutaneous tissue of nude mice is profoundly related to their FN-degrading capability. This capability may be catalyzed by uPA and/or metal-dependent serine proteinase-like proteases of 75 and 68 kDa.
研究了人胃癌细胞系（MKN45和MKN28）在裸鼠皮下组织中的侵袭性以及细胞外基质（ECM）的降解能力。MKN45细胞比MKN28细胞更具侵袭性。免疫染色显示肿瘤周围有密集的层状纤连蛋白（FN）积聚。然而，在侵袭性MKN45生长前沿，FN纤维是不连续的和/或完全消失；MKN28肿瘤未显示FN纤维断开。除FN外的ECM成分从未显示出如此大量的肿瘤周围积聚。人成纤维细胞与MKN45细胞共培养，比与MKN28细胞共培养更明显地显示出与每个肿瘤接触的成纤维细胞产生的FN降解。两种细胞系在无血清培养中都产生几种FN降解酶。MKN45培养基中的蛋白酶在尿激酶型纤溶酶原激活剂（uPA）和分子量（MW）为75和68 kDa的金属依赖性丝氨酸蛋白酶样蛋白酶方面比MKN28培养基中的蛋白酶更具活性。还从MKN45培养基中检测到I型胶原降解48 kDa蛋白酶，但未从MKN28培养基中检测到。MKN28细胞分泌其他种类的FN降解酶，估计分子量约为29和100 - 150 kDa。我们发现这两种细胞系在产生ECM成分的能力或粘附于纯化ECM成分的能力方面没有明显差异。从这些结果我们得出结论，这些细胞向裸鼠皮下组织的基质侵袭与其FN降解能力密切相关。这种能力可能由uPA和/或分子量为75和68 kDa的金属依赖性丝氨酸蛋白酶样蛋白酶催化。
