卵巣癌転移に関わる免疫機構の解明

阐明卵巢癌转移中涉及的免疫机制

• 批准号: 16J07245
• 负责人: 植野 さやか
• 金额: $ 1.22万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2016
• 资助国家: 日本
• 起止时间: 2016-04-22 至 2018-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16J07245/
• 关键词: 腹腔内播種; 免疫抑制; 卵巣癌; 転移; 免疫回避; 癌幹細胞

昨年度の研究結果から、卵巣癌幹細胞はEpCAMの発現によって放出された液性因子によりマクロファージを誘引し、免疫機構の制御及び腹腔内播種を引き起こすことが示唆された。今年度はさらに癌幹細胞だけでなく、卵巣癌細胞全体を対象に免疫回避機構を解析することとした。マウス卵巣癌細胞株をマウス腹腔内移植を繰り返して高転移株を作成した。次に、高転移株と親株の遺伝子発現をマイクロアレイにて比較し、転移に関わる候補遺伝子を抽出した。さらに、公共データベースを用いて卵巣癌患者予後に寄与する候補遺伝子を絞り込み、SERPINF1（タンパク：PEDF）を同定した。PEDFは他の癌種においては、血管新生抑制機能を介して癌抑制遺伝子として作用することが知られているが、卵巣癌における機能は明らかになっていない。今回の検討では、PEDFは高転移株で発現が増強しており、ヒトデータベースの解析においても、発現の高い群で予後不良であるとの結果であった。そこでPEDFが実際に転移に寄与しているかどうかを調べることとした。まず、PEDFを親株細胞に強制発現させると、腹腔内転移が増加した。親株細胞の中にはPEDFの発現の異なる多数のクローンが含まれており、PEDF発現強度に応じて腹腔内転移能が増加した。また、PEDFの発現は足場の有無に関わらず、増殖に影響を及ぼさない一方、がん細胞の腹腔内での生存期間に影響を与えた。腹腔内の免疫細胞解析では、IL10を産生するCD206+マクロファージが増加しており、腹腔内IL10濃度自体も有意に増加することを見出した。これらの結果より、卵巣癌細胞から放出されるPEDFは腹腔内免疫細胞を抑制し、癌細胞の生存ひいては腹腔内転移能の獲得に寄与していることが示唆された。

According to the results of last year's study, the EpCAM of ovarian cancer cells showed the release of liquid factors, immune control and intraperitoneal inoculation. This year, the whole population of cancer cells and ovary cancer cells were analyzed by the immune avoidance mechanism. The ovary cancer cell line was implanted into the abdominal cavity, and the high-grade transplant was made. The secondary and high transplant plants show that the children of the secondary and high transplant plants are not in the first place, and that they are waiting to be pulled out. Please send the message to the patient with egg cancer in the future and send it to the patient in the same way as the child in the hospital, SERPINF1 (doctor: PEDF). PEDF and angiogenesis inhibitors can detect the effects of cancer suppressants and ovary cancers. This time, the high-level transplant of PEDF showed that the results showed that the bad results were not good. Please send me a copy of the PEDF message and send it to you. The cells of mice and PEDF strains were forced to observe the disease, and the intra-abdominal cavity was transferred into the abdominal cavity. In the cells of the plant, PEDF showed that most of the cells contained the strength of PEDF, and increased the energy transfer in the abdominal cavity. It is found that there are no drugs in the market, either in the host, in the host, or in the abdominal cavity during the life cycle of the recipient and PEDF. The immune cells in the abdominal cavity were analyzed, the immune cells in the abdominal cavity were detected by IL10, the immune cells in the abdominal cavity were analyzed, the immune cells were analyzed in the abdominal cavity, the immune cells were analyzed in the abdominal cavity, the immune cells were analyzed in the abdominal cavity, the immune cells were analyzed in the abdominal cavity, the immune cells were analyzed in the abdominal cavity, and the IL10 concentration in the abdominal cavity was deliberately increased. The results showed that the ovarian cancer cells released immune suppression in the abdominal cavity of PEDF, and the survival rate of the cancer cells was significantly higher than that of the control group (P < 0.01).