Role of chemokine systems and its relation to immunotolerance and angiogenesis in ovarian cancer progression

• Project/Area Number: 26462535
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Wakayama Medical University
• Principal Investigator: INO Kazuhiko 和歌山県立医科大学, 医学部, 教授 (60303640)
• Co-Investigator(Kenkyū-buntansha): 近藤 稔和 和歌山県立医科大学, 医学部, 教授 (70251923) ; 馬淵 泰士 和歌山県立医科大学, 医学部, 助教 (80382357)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 婦人科腫瘍 / 卵巣癌 / ケモカイン / 血管新生 / 免疫寛容 / ノックアウトマウス / 腫瘍免疫 / 腹膜播種 / 腫瘍微小環境 / マクロファージ

Outline of Final Research Achievements

Interaction between tumor and stromal cells through chemokine systems was essential for cancer progression. The purpose of this study is to explore the pathophysiological roles of CX3CL1-CX3CR1 and CCR5 systems in ovarian cancer progression. A murine ovarian cancer cell line ID8 was used. When ID8 cells were inoculated to WT and Cx3cr1-/- mice, Cx3cr1-/- mice survived significantly longer than WT ones, and the tumor number in the abdominal cavity was significantly reduced in Cx3cr1-/- mice. Similarly, when ID8 cells were inoculated to WT and Ccr5-/- mice, tumor dissemination in abdominal cavity and tumor angiogenesis were significantly suppressed in Ccr5-/-mice compared with WT mice. These findings suggest that these chemokine networks are essential for ovarian cancer progression, and that CX3CR1 and CCR5 systems might be candidate molecules for a novel targeted therapy of ovarian cancer.

Research Products

• [Journal Article] Downregulation of indoleamine 2, 3-dioxygenase expression in the villous stromal endothelial cells of placentas with preeclampsia (2017)
  • Author(s): Iwahashi N, Yamamoto M, Nanjo S, Toujima S, Minami S, Ino K
  • Journal Title: J Reprod Immunol Volume: 119 Pages: 54-60
  • DOI: 10.1016/j.jri.2017.01.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Primary tumor SUV(max) on preoperative FDG-PET/CT is a prognostic indicator in stage IA2-IIB cervical cancer patients treated with radical hysterectomy (2016)
  • Author(s): Yagi S, Yahata T, Mabuchi Y, Tanizaki Y, Kobayashi A, Shiro M, Ota N, Minami S, Terada M, Ino
  • Journal Title: Mol Clin Oncol Volume: 5 Pages: 216-222
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prognostic impact of primary tumor SUV(max) on preoperative (18)F-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography in endometrial cancer and uterine carcinosarcoma (2016)
  • Author(s): Yahata T, Yagi S, Mabuchi Y, Tanizaki Y, Kobayashi A, Yamamoto M, Mizoguchi M,Nanjo S, Shiro M, Ota N, Minami S, Terada M, Ino K
  • Journal Title: Mol Clin Oncol Volume: 5 Pages: 467-474
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] AG490, a Jak2 inhibitor, suppressed the progression of murine ovarian cancer. (2015)
  • Author(s): Kobayashi A, Tanizaki Y, Kimura A, Ishida Y, Nosaka M, Toujima S, Kuninaka Y, Minami S, Ino K, Kondo T.
  • Journal Title: Eur. J. Pharmacol. Volume: 766 Pages: 63-75
  • DOI: 10.1016/j.ejphar.2015.09.039
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathologic Factors of Cervical Adenocarcinoma Stages IB to IIB (2015)
  • Author(s): Mabuchi Y, Yahata T, Kobayashi A, Tanizaki Y, Shiro M, Ota N, Yagi S, Minami S, Ino K
  • Journal Title: Int J Gynecol Cancer Volume: 25 Issue: 9 Pages: 1677-1682
  • DOI: 10.1097/igc.0000000000000542
  • Peer Reviewed
• [Journal Article] Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment. (2014)
  • Author(s): Tanizaki Y(1), Kobayashi A, Toujima S, Shiro M, Mizoguchi M, Mabuchi Y, Yagi S, Minami S, Takikawa O, Ino K.
  • Journal Title: Cancer Sci. Volume: 105 Issue: 8 Pages: 966-73
  • DOI: 10.1111/cas.12445
  • Peer Reviewed / Open Access
• [Journal Article] Ovarian steroid cell tumor, not otherwise specified, producing testosterone (2014)
  • Author(s): Mizoguchi M, Minami S, Yamamoto M, Tanizaki Y, Kobayashi A, Ino K
  • Journal Title: J Obstet Gynaecol Res Volume: 40 Issue: 9 Pages: 2081-2085
  • DOI: 10.1111/jog.12467
  • Peer Reviewed / Open Access
• [Presentation] Decreased expression of idoleamine 2.3-dioxygenase in villous stromal cells of placentas with preeclampsia and/or fetal growth restriction (2016)
  • Author(s): Iwahashi N, Ino K.
  • Organizer: IFPA Meeting 2016 in Portland
  • Place of Presentation: Portland , USA
  • Year and Date: 2016-09-13
  • Int'l Joint Research
• [Presentation] CX3CL1-CX3CR1システムは腫瘍随伴マクロファージの動員を介して卵巣癌腹膜播種を促進する (2015)
  • Author(s): 谷﨑優子，小林彩，溝口美佳，城道久，太田菜美，馬淵泰士，八木重孝，南佐和子，井箟一彦
  • Organizer: 第67回日本産科婦人科学会
  • Place of Presentation: 横浜
  • Year and Date: 2015-04-10 – 2015-04-12
• [Presentation] 卵巣癌の増殖・進展におけるCCR5の病態生理学的役割についての検討 (2014)
  • Author(s): 小林彩，谷﨑優子，瀧口義弘，馬淵泰士，八木重孝，南佐和子，井箟一彦
  • Organizer: 第56回日本婦人科腫瘍学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2014-07-17 – 2014-07-19