Interleukin-8 is a possible angiogenic factor in endometrial cancer

Interleukin-8 可能是子宫内膜癌的血管生成因子

• 批准号: 08457442
• 负责人: TERAKAWA Naoki
• 金额: $ 3.65万
• 依托单位: Tottori University (School of Medicine)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457442/
• 关键词: Endometrial cancer; Angiogenic factor; Tumor necrosis factor a; Interleukin-8; Stromal cells; Microvessel density; Cancer growth; Paracrine effect; 子宮内膜; 子宮内膜症; 細胞増殖; IL-8; TNFα

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

本研究旨在寻找子宫内膜癌中血管生成因子S的候选基因。近年来的临床研究发现，子宫内膜异位症患者腹腔液中肿瘤坏死因子-α(TNF-a)浓度升高，且与白介素8(IL-8)水平呈显著正相关。因此，我们研究了血管生成因子--肿瘤坏死因子α和白介素8对采集自正常子宫内膜、子宫内膜异位症和子宫内膜癌组织的间质细胞的影响。在培养液中加入肿瘤坏死因子α(0-100pg/ml)可增加子宫内膜和子宫内膜间质细胞产生IL-8，且呈剂量依赖关系。四甲基偶氮唑盐比色法显示，在肿瘤坏死因子α存在的情况下，异位内膜基质细胞的数量增加，但加入抗IL-8抗体后，肿瘤坏死因子α对细胞增殖的刺激作用消失。IL-8(200pg/ml)对EN-…间质细胞有促生长作用子宫内膜癌较多，为对照的130%。用逆转录聚合酶链式反应和Southern印迹法检测各间质细胞中肿瘤坏死因子α受体II和白细胞介素8受体A的转录产物的表达。对子宫内膜癌切除标本进行第八因子相关抗原和抗白细胞介素8抗体的免疫组织化学染色，光镜下计数第八因子相关抗原微血管数和每一面积的白介素8染色血管数。低分化癌中中、低分化的微血管和IL-8染色的微血管数显著增加，提示微血管和IL-8阳性的血管密度与肿瘤分级有关。综上所述，这些结果表明，肿瘤坏死因子α对子宫内膜癌间质细胞和内皮细胞都有旁分泌作用，并刺激IL-8的产生。本研究还提出了IL-8在子宫内膜癌中可能作为血管生成因子，促进肿瘤生长的可能性。较少

项目成果

H.Itamochi: "Antitumor Effects of Internal Iliac Arterial Infusion of Platinum Compounds in a Rabbit Cervical Cancer Model" Obstet Gynecol. 89・2. 286-290 (1997)

H.Itamochi：“兔宫颈癌模型中髂内动脉输注的抗肿瘤作用”Obstet Gynecol 89・2（1997）。

Junzo Kigawa: "Glutathione concentration may be a useful predictor of response to second-line chemotherapy in patients with ovarian cancer." Cancer. 82 (4). 692-702 (1998)

Junzo Kikawa：“谷胱甘肽浓度可能是卵巢癌患者对二线化疗反应的有用预测因子。”

Xiusi Cheng: "Glutathione S-transferase-pi expression and glutathione concentration in ovarian carcinoma before and after chemotherapy." Cancer. 79 (3). 521-527 (1997)

程秀思：“卵巢癌化疗前后谷胱甘肽S-转移酶-pi的表达及谷胱甘肽浓度”。

Yukihisa Minagwa: "Enhanced topoisomerase I activity and increased topoisomerase II _α content in cisplatin-resistant cancer cell line." Jpn.J.Cancer.Res.88 (12). 1218-1223 (1997)

Yukihisa Minagwa：“顺铂耐药癌细胞系中拓扑异构酶 I 活性增强，拓扑异构酶 II _α 含量增加。”Jpn.J.Cancer.Res.88 (1218-1223)。

Tasuku Harada: "Increased interleukin-6 levels in peritoneal fluid of infertile patients with active endometriosis." Am.J.Obstet.Gynecol.176 (3). 593-597 (1997)

Tasuku Harada：“患有活动性子宫内膜异位症的不孕患者腹腔液中白细胞介素 6 水平升高。”