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TNFSF15表达下调或缺失是卵巢癌组织中肿瘤新血管形成的前提条件

张秋月,顾欣,许静静,李凤舞,谷超,邓为民   

  1. 天津医科大学免疫教研室
  • 收稿日期:2011-10-31 修回日期:2012-02-08 出版日期:2012-09-15 发布日期:2012-09-15
  • 通讯作者: 张秋月

Downregulation or absent of TNFSF15 in Ovarian Cancer Is a Pre-requisite for Tumor Neovascularization

  • Received:2011-10-31 Revised:2012-02-08 Published:2012-09-15 Online:2012-09-15

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摘要： 摘要 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其与卵巢癌临床分期的关系，并探讨在小鼠体内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卵巢组织(12例)、卵巢癌组织(94例)中TNFSF15蛋白表达情况并对其进行统计学分析；采用C57BL/6荷瘤小鼠腹腔注射重组TNFSF15蛋白和以TNFSF15-shRNA干扰其内源性表达的方法，观察其对小鼠卵巢癌细胞系ID8在同基因小鼠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，TNFSF15在卵巢癌组织标本中表达低下甚至缺失（P<0.001），且其表达水平与卵巢癌病人的临床分期呈负相关（P<0.005）；动物体内实验结果显示，重组TNFSF15蛋白腹腔注射显著抑制ID8细胞在C57BL/6体内的生长（P<0.05）；而以TNFSF15-shRNA干扰其内源性表达后则会加速ID8细胞的生长（P<0.05）。结论：卵巢癌微环境中TNFSF15的表达下调或缺失是肿瘤新血管形成的前提条件。

关键词: TNFSF15, 卵巢癌, 肿瘤, 新血管形成, ID8细胞系

Abstract: Abstract Objective: To study the expression of tumor necrosis factor superfamily-15 (TNFSF15) in human ovarian cancer specimens, and it’s relationship with the clinical staging. Furthermore, we mean to study the effects of TNFSF15 on tumor angiogenesis and growth in vivo. Methods: The expression of TNFSF15 in ovary tissue specimens (12 normal and 94 ovarian cancer) were detected by immunohistochemistry assay. We used recombinant TNFSF15 to treat ID8-bearing C57BL/6 mice via intraperitoneal injection or used TNFSF15-shRNA to knock down its expression in tumor microenvironment, and then the influences on tumor angiogenesis and growth were assessed. Results：Compared to the normal ovary tissues, the expression of TNFSF15 was low or absent in the cancer specimens（P<0.001）and TNFSF15 levels are inversely correlated to the clinical stages of human ovarian cancer（P<0.005）. Using a mouse syngeneic tumor model, we demonstrated that recombinantNFSF15 markedly inhibited the growth of ID8 tumors（P<0.05）; on the other hand, TNFSF15-shRNAadministration could accelerate the growth of ID8 tumors（P<0.05）. Conclusion: TNFSF15 downregulation or absent in ovarian cancer microenvironment is a pre-requisite for tumor neovascularization and tumor growth.

Key words: ovarian cancer, tumor, neovascularization, ID8 cell lines