摘要目的 研究血管内皮生长因子C(VEGF-C)与基质金属蛋白酶(MMP)-2、MMP-9在乳腺癌组织中的表达及三者在乳腺癌淋巴结转移中的作用.方法 应用免疫组织化学SP法对84例乳腺癌(有腋淋巴结转移者52例,无腋淋巴结转移者32例)的VEGF-C、MMP-2和-9以及血管内皮透明质酸受体-1(LYVE-1)的表达进行检测,统计分析VEGF-C、MMP-2和-9与乳腺癌淋巴管生成的关系.利用重组质粒表达载体介导的短发夹式干扰RNA(shRNA)靶向沉默乳腺癌MCF-7细胞株中VEGF-C基因,PCR检测VEGF-C、MMP-2和-9的表达.结果 VEGF-C与MMP-2和-9在乳腺癌组织中均呈过表达,分别为83.3%(70/84)、89.3%(75/84)和75.0%(63/84),且在腋淋巴结转移组[94.2%(49/52)、98.1%(51/52)和88.5%(46/52)]比无淋巴结转移组[65.6%(21/32)、75.0%(24/32)和53.1%(17/32)]明显高表达(P＜0.05);淋巴管密度在腋淋巴结转移组及无转移组的表达有统计学意义(P＜0.05),随着VEGF-C与MMP-2和-9表达强度增加,淋巴管数量也增加(P＜0.05);转染重组质粒后MCF-7细胞株的VEGF-C及MMP-2和-9的mRNA表达水平下调,抑制率分别为95.0%、53.0%和77.0%(P＜0.05).结论 VEGF-C与MMP-2和-9协同促进乳腺癌组织的淋巴管新生和乳腺癌淋巴结转移.

abstractsObjective To study the expression of matrix metalloproteinase(MMP)-2,MMP-9 and vascular endothelial growth factor(VEGF)-C in breast cancer and their role in lymph node metastasis.Methods Immunohistochemical staining was used to detect the expression of VEGF-C,MMP-2,MMP-9 and LYVE-1 in 84 cases of breast cancer.including 52 cases with and 32 cases without lymph node metastases.The recombinant vector(pSIREN-VEGF-C)was transfected into human breast cancer cell MCF-7 by liposome,and the RNA expression of MMP-2,MMP-9 and VEGF-C in MCF-7 cells after transfection was detected by PCR.Results The expressions of MMP-2,MMP-9 and VEGF-C were 98.1%(51/52),88.5%(46/52),and 94.2%(49/52)respectively for the metastatic group,and 75.0%(24/32),53.1%(17/32),and 65.6%(21/32)respectively for the non metastatic group,and there was significant difference between these groups (P＜0.05).The lymphatic vessel density between these two groups was also significantly different(P＜0.05).Increased expression of MMP-2,MMP-9 and VEGF-C was also associated with increased number of lymphatic vessels had also increased(P＜0.05).The expression of MMP-2,MMP-9 and VEGF-C in MCF-7 cells after gene transfection decreased significantly(P＜0.05).Conclusion MMP-2 and MMP-9 in conjunction with VEGF-C,promote lymphangiogenesis and lymph node metastasis of breast cancer.