肺癌H460细胞与胚肺成纤维细胞相互作用对基质金属蛋白酶-2的表达影响

目的：研究肺癌H460细胞和胚肺成纤维细胞相互作用对基质金属蛋白酶-2（MMP-2）表达的影响．方法：在单层平面培养条件下，H460细胞和胚肺成纤维细胞条件培养基或胚肺成纤维细胞和H460细胞条件培养基共同培养，胚肺成纤维细胞分别按1：1，1：2，1：4，1：8与H460细胞共同培养．三维胶原立体培养条件下，H460细胞和胚肺成纤维细胞共同培养，72h后明胶酶谱法测定培养基中MMP-2的表达．结果：胚肺成纤维细胞条件培养基不能促进H460细胞MMP-2酶原和活化酶的表达，但H460细胞条件培养基能促进胚肺成纤维细胞MMP-2酶原和活化酶的表达．胚肺成纤维细胞分别按1：1，1：2，1：8与肺癌H460细胞时共同培养时，MMP-2酶原和活化酶的表达均增强；按1：4与肺癌H460细胞共同培养时MMP-2酶原表达有所增加，但活化酶未见改变．三维胶原立体H460细胞和胚肺成纤维细胞共同培养时MMP-2酶原和活化酶的表达均增强且高于单层平面培养．结论：肺癌H460细胞与胚肺成纤维细胞相互作用能通过上调MMP-2的表达和活化影响肺癌侵袭和转移．

Influence of interactions between lung cancer cells and fetal lung fibroblast on matrix metalloproteinase-2 expression

AIM： To investigate the influence of interactions between lung cancer cell H460 and fetal lung fibroblasts on matrix metalloproteinase-2 （ MMP-2 ） expression. METHODS ： H460 cells with condition medium derived from fetal lung fibroblasts or fetal lung fibroblasts with condition medium derived from H460 cells were incubated in monolayer culture model. Fetal lung fibro- blasts and H460 cells at 1 ： 1, 1 ： 2, 1 ： 4 and 1 ： 8 cell ratios were co-cultured in monolayer culture model. H460 cells with fetal lung fibroblasts were co-cultured in three dimensional collagen gels. After 72 hours, the activity and expression of MMP-2 in the condition medium were studied by gelatin zymography. RESULTS： The condition medium derived from H460 cells stimulated proMMP-2 and MMP-2 expression while the condition medium derived from fetal lung fibroblasts failed to stimulate proMMP-2 and MMP-2 of H460 cells. When fetal lung fibroblast and H460 cells were co-cultured at 1 ： 1, 1 ： 2 and 1 ： 8 cell ratios, the levels of both proMMP-2 and MMP-2 were enhanced and at 1：4 only the levels of pro-MMP-2 were enhanced. H460 cells cultured with fetal lung fibroblasts resulted in the production of proMMP-2 and MMP-2 and the production in three dimensional collagen gels was higher than that in monolayer culture model. CONCLUSION： The interactions between lung cancer cell H460 and fetal lung fibro- blasts may influence lung cancer invasion and metastasis through up-regulating MMP-2 secretion and activation.