Interleukin-8 is a possible angiogenic factor in endometrial cancer

本研究旨在发现子宫内膜癌中一种候选血管生成因子。在近期的临床研究中，我们发现子宫内膜异位症患者腹膜液中肿瘤坏死因子a （tumor necrosis factor a, TNF a）浓度升高，且TNF a与白细胞介素-8 （interleukin-8, IL-8）水平存在显著相关性。因此，我们研究了血管生成因子TNF a和IL-8对从正常子宫内膜、子宫内膜异位症和子宫内膜癌组织中收集的基质细胞的影响。在培养基中添加TNF a （0-100pg/ml）可增加子宫内膜和子宫内膜异位症基质细胞中IL-8的产生，且呈剂量依赖性。MTT实验显示，TNF a存在时，子宫内膜异位症间质细胞数量增加，但抗il -8抗体的加入消除了TNF a对细胞增殖的刺激作用。IL-8 （200pg/ml）对en…More子宫内膜癌间质细胞有促进生长的作用，为对照组的130%。RT-PCR和Southern blot检测各组间质细胞中TNF - a受体II和IL-8受体a型转录本的表达。对子宫内膜癌子宫切除术标本进行viii因子相关抗原和抗il -8抗体免疫组化染色，光镜下计数每面积viii因子相关抗原微血管数量和il -8染色血管数量。中、低分化癌微血管数量及低分化癌IL-8染色血管数量均显著增加，提示微血管及IL-8阳性血管密度与肿瘤分级相关。综上所述，这些结果表明TNF a对子宫内膜癌的基质细胞和内皮细胞都有旁分泌作用，并刺激IL-8的产生。本研究也提示IL-8可能在子宫内膜癌中作为血管生成因子，促进肿瘤生长。少

This study was undertaken to find out the candidate of an angiogenic factor (s) in endometrial carcinoma. In recent clinical studies, we have found that the concentration of tumor necrosis factor a (TNF a) in peritoneal fluid of patients with endometriosis was increased and there was a significant correlation between the peritoneal fluid levels of TNF a and interleukin-8 (IL-8). We, therefore, examined the effects of angiogenic factors, TNF a and IL-8, on stromal cells collected from normal endometrium, endometriosis and endometrial carcinoma tissues. Addition of TNF a (0-100pg/ml) to the culture medium increased the production of IL-8 in both endometrial and endometriotic stromal cells, in a dose-dependent manner. The MTT assay showed that the number of endometriotic stromal cells increased in the presence of TNF a, but addition of anti-IL-8-antibody abolished the stimulating effect of TNF a on cell proliferation. IL-8 (200pg/ml) showed a growth-promoting effect on stromal cells of en … More dometrial carcinoma, which was 130% of control values. The expression of transcripts of TNF a receptor II and IL-8 receptor typeA were observed in each stromal cells by RT-PCR and Southern blot analysis.Hysterectomy specimens of endometrial cancer were stained immunohistochemically for factor VIII-related antigen and anti-IL-8-antibody, and the numbers of the factor VIII-related antigen microvessels and the IL-8-stained vessels per area were counted by light microscopy. The numbers of microvessels in moderately-and poorly differentiated and those of IL-8 stained vessels in poorly differentiated carcinoma were significantly increased, suggesting that microvessel and IL-8-positive vessel densities are correlated with tumor grade. In summary, these results suggest that TNF a exerts paracrine effects on both the stromal and endothelial cells of endometrial carcinoma and stimulates the production of IL-8. The present study also raise the possibility that IL-8 may act as an angiogenic factor in endometrial cancer and promote the cancer growth. Less