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目的:基质金属蛋白酶能够降解细胞外基质和基底膜,在肿瘤的浸润和转移过程中起重要作用。研究基质金属蛋白酶-2(matrixmetallopro-teinase2,MMP-2)及其mRNA在乳腺癌组织和细胞中的表达,探讨其与血管生成及肿瘤生物学行为的关系。方法:实验于2002-01/2004-01在吉林大学基础医学院病理生物学教育部重点实验室完成。应用免疫组织化学、免疫细胞化学、原位杂交、侵袭实验、明胶酶谱分析及形态定量分析方法,对76例乳腺癌组织和体外培养的MCF-7细胞中MMP-2及其mRNA、微血管密度(MVD)进行检测。结果:乳腺癌组织中MMP-2及其mRNA的表达均高于癌旁正常组织;MMP-2及其mRNA主要表达于肿瘤细胞胞浆中,其阳性率分别为77.63%和71.05%;MMP-2及其mRNA的表达均与乳腺癌组织学分级、淋巴结转移密切相关。MVD与乳腺癌组织学分级、淋巴结转移密切相关。MMP-2或其mRNA表达阳性组MVD值明显高于阴性组。MCF-7细胞中MMP-2及其mRNA均为阳性;MMP-2抗体可使MCF-7细胞侵袭细胞数由(56.21±3.68)个/400倍下降为(20.32±3.24)个/400倍;直接培养于培养瓶的MCF-7细胞可以分泌MMP-2酶原,培养于I型胶原包被培养瓶的MCF-7细胞MMP-2酶原表达增强并且出现活化形式。结论:乳腺癌组织和细胞具有较强的分泌MMP-2的能力,MMP-2促进肿瘤的侵袭和转移,
OBJECTIVE: Matrix metalloproteinases (MMPs) can degrade extracellular matrix and basement membrane and play an important role in tumor invasion and metastasis. To investigate the expression of matrixmetalloprotein-2 (MMP-2) and its mRNA in breast cancer tissues and cells, and to explore its relationship with angiogenesis and tumor biological behavior. Methods: The experiment was performed at Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University from January 2002 to January 2004. Immunohistochemistry, immunocytochemistry, in situ hybridization, invasion assay, gelatin zymography and morphometric analysis were used to detect the expression of MMP-2 and its mRNA, microvessel density (MVD) in 76 breast cancer tissues and MCF-7 cells cultured in vitro (MVD) for testing. Results: The expression of MMP-2 and its mRNA in breast cancer tissues was higher than that in adjacent normal tissues. The expression of MMP-2 and its mRNA was mainly in the cytoplasm of tumor cells, the positive rates were 77.63% and 71.05% 2 and its mRNA expression were closely related to breast cancer histological grade, lymph node metastasis. MVD and breast cancer histological grade, lymph node metastasis are closely related. The MVD of MMP-2 or its mRNA positive group was significantly higher than that of negative group. The number of invasive cells in MCF-7 cells decreased from (56.21 ± 3.68) / 400 times to (20.32 ± 3.24) / 400 times in MCF-7 cells, The MCF-7 cells directly cultured in culture flasks can secrete MMP-2 zymogen, the expression of MMP-2 zymogen in MCF-7 cells cultured in type I collagen coated flasks is enhanced and the activated forms appear. Conclusion: Breast cancer tissues and cells have a strong ability to secrete MMP-2, MMP-2 promotes tumor invasion and metastasis,