【摘要】 目的:研究Osteoglycin表达与肿瘤细胞分泌基质金属蛋白酶(matrix metalloproteinases,MMPs)的关系。方法:构建真核表达载体pIRESpuro3 Osteoglycin(+),将其转染至高淋巴道转移能力小鼠肝癌Hca-F细胞,接种于615小鼠皮下,体内试验评价转移能力;同期采用酶谱法体外试验评价不同环境中Hca-F细胞表达Osteoglycin与其分泌MMPs的关系。结果:转染pIRESpuro3 Osteoglycin(+)的Hca-F细胞Osteoglycin在mRNA和蛋白水平表达显著增高,体内试验显示,其外周淋巴结转移率明显降低(P=0.028);体外试验表明,转染Osteoglycin基因显著降低了Hca-F细胞淋巴环境中MMPs分泌能力(P<0.05或P<0.01),然而未能影响肝匀浆或脾匀浆环境或DMEM培养基中肿瘤细胞MMPs分泌能力。结论:高表达Osteoglycin降低小鼠肝癌Hca-F细胞淋巴环境中MMPs分泌能力,抑制肿瘤细胞MMPs分泌能力可能是Osteoglycin调控肿瘤淋巴道转移机制之一。更多还原

【Abstract】 Objective:To investigate the possible correlation between osteoglycin expression and matrix metallopro- teinase(MMP)activity in tumor cells.Methods:A eukaryotic expression plasmid pIRESpuro3 osteoglycin(+) was constructed and transfected into mouse hepatocarcinoma Hca-F cells with high metastatic potential.In vi- vo tumor metastasis assay was employed to evaluate the contribution of osteoglycin expression to the malig- nant behavior of Hca-F and zymographic analysis was used to observe the possible correlation between os- teoglycin expression and MMP activity of Hca-F cells cultured with different condition.Results:Hca-F cells transfected with pIRESpuro3 osteoglycin(+)produced effective and stable expression of osteoglycin at mR- NA and protein levels.Lymphatic metastasis rate was decreased in tumor burden mice(P=0.028).High ex- pression of osteoglycin decreased MMPs activity of Hca-F cells cultured with extract of lymph node(P<0.05 or P<0.01)but didn’t influence MMPs activity of Hca-F cells cultured with liver or spleen extract or DMEM medium.Conclusion:High expression of osteoglycin can decrease MMPs activity in Hca-F cells cultured with extract of lymph node.Regulation of MMPs activity might be one of the mechanisms that osteoglycin can suppress lymphatic metastasis.更多还原