TNFSF15表达下调或缺失对卵巢癌组织中肿瘤新血管形成的影响

目的:探讨肿瘤坏死因子超家族-15(TNFSF15)在人卵巢癌标本中的表达及在小鼠体内TNFSF15对卵巢癌血管生成及卵巢癌生长的影响。方法:应用免疫组化法检测正常组(12例)、卵巢癌组(94例)中TNFSF15的表达情况及微血管密度(MVD);雌性C57BL/6小鼠24只随机分为对照组、重组TNFSF15注射组(实验组)、TNFSF15-shRNA处理组(A组)、shRNA-对照组(B组),每组6只,各组均采用皮下注射ID8细胞制备小鼠荷瘤模型,实验组采用腹腔注射重组TNFSF15蛋白,A、B组采用TNFSF15-shRNA干扰其内源性表达的方法,通过检测小鼠肿瘤组织MVD值并测量肿瘤体积大小,观察其对小鼠卵巢癌细胞系ID8在小鼠C57BL/6体内血管生成及肿瘤生长的影响。结果:与正常卵巢组织相比,卵巢癌组织标本中TNFSF15表达显著降低(P<0.01),且Ⅲ/Ⅳ期TNFSF15阳性表达率较Ⅰ/Ⅱ期降低(P<0.05);实验组较对照组小鼠肿瘤组织中MVD值降低且肿瘤体积减小(P<0.05),而A组较B组MVD值升高且肿瘤体积增大(P<0.05)。结论:卵巢癌微环境中TNFSF15表达下调或缺失是肿瘤新血管形成的前提条件。

The Effect of Down Regulation of TNFSF15 on Tumor Neovascularization of Ovarian Cancer

Objective:To study the expression of tumor necrosis factor superfamily-15(TNFSF15) in human ovarian cancer specimens and the effects of TNFSF15 on tumor angiogenesis and growth in mice.Methods:The expression of TNFSF15 and the value of microvessel density(MVD) were detected by the method of immunohistochemistry in normal ovary group(n=12) and ovarian cancer group(n=94).Twenty-four female C57BL/6 mice were randomly divided into 4 groups:control group,recombinant TNFSF15-treated group(experimental group),TNFSF15 shRNA-treated group(group A) and control-shRNA(group B).There were 6 mice for each group.The tumor-bearing mouse model was made by injecting subcutaneously ID8 cells into the flank of mia.The recombinant TNFSF15 was used to treat ID8-bearing C57BL/6 mice via intraperitoneal injection.TNFSF15-shRNA was used in group A and group B.The influences of TNFSF15 on tumor angiogenesis and growth were assessed by measuring MVD values and tumor volumes in mice.Results:Compared to the normal ovary tissues,the expression level of TNFSF15 decreased significantly in cancer specimens(P < 0.01),and the positive expression of TNFSF15 protein was lower in stage Ⅲ/Ⅳ than that of stage Ⅰ/Ⅱ(P < 0.05).The values of MVD and the tumor volumes were decreased in experimental group than those of control group(P < 0.05).On the other hand,the MVD values and tumor volumes were higher in group A than those of group B(P < 0.05).Conclusion:The down regulation or absent of TNFSF15 in ovarian cancer microenvironment is a pre-requisite for tumor neovascularization.