A novel mechanism of the peritoneal dissemination via multiple network among cellular skeleton-related molecules in ovarian cancer

• Project/Area Number: 15K15604
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Nagoya University
• Principal Investigator: Kajiyama Hiroaki 名古屋大学, 医学系研究科, 准教授 (00345886)
• Co-Investigator(Renkei-kenkyūsha): SENGA Takeshi 名古屋大学, 大学院医学系研究科, 准教授 (80419431)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 卵巣癌 / 腹膜播種 / 腹膜中皮細胞 / 腹膜間隙透過性 / filopodia形成 / 細胞コミュニケーション / アクチンモーター蛋白 / 浸潤

Outline of Final Research Achievements

Epithelial ovarian carcinoma (EOC) is believed to cause peritoneum dissemination through microenvironmental cell-to-cell communication between the tumor and mesothelium, leading to the further acquisition of progressive and metastatic potentials. In the present study, we aimed to determine the role of cancer-associated mesothelial cells (CAMCs) in the maintenance of cisplatin-resistance. Normal mesothelium (MC) showed an epithelial morphology with a cobblestone appearance. When MCs were co-cultured with malignant ascites from patients with advanced EOC, a dramatic morphologic change was noted from an epithelioid pattern to a-SMA-positive fibroblastic, mesenchymal pattern. Our findings indicate the possible involvement of CAMCs in the maintenance of cisplatin-resistance, resulting in being “seeds of recurrence”. The novel mechanism of CAMCs as a facilitator of EOC progression is displayed through microenvironmental cell-to-cell communication between EOC and the mesothelium.

Research Products

• [Journal Article] Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer. (2017)
  • Author(s): Yokoi A, Yoshioka Y, Yamamoto Y, Ishikawa M, Ikeda SI, Kato T, Kiyono T, Takeshita F, Kajiyama H, Kikkawa F,
  • Journal Title: Nat Commun. Volume: 6 Issue: 1 Pages: 14470-14470
  • DOI: 10.1038/ncomms14470
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Murine Experimental Model of Original Tumor Development and Peritoneal Metastasis via Orthotopic Inoculation with Ovarian Carcinoma Cells. (2016)
  • Author(s): Koya Y, Kajiyama H, Liu W, Shibata K, Senga T, Kikkawa F.
  • Journal Title: J Vis Exp. Volume: 118 Issue: 118 Pages: 407-414
  • DOI: 10.3791/54353
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of glypican-3-derived peptide vaccine therapy on the survival of patients with refractory ovarian clear cell carcinoma. (2016)
  • Author(s): Suzuki S, Sakata J, Utsumi F, Sekiya R, Kajiyama H, Shibata K, Kikkawa F, Nakatsura T.
  • Journal Title: Oncoimmunology Volume: 5 Issue: 11 Pages: e1238542-e1238542
  • DOI: 10.1080/2162402x.2016.1238542
  • Peer Reviewed / Open Access
• [Journal Article] PRIMA-1MET induces apoptosis through accumulation of intracellular reactive oxygen species irrespective of p53 status and chemo-sensitivity in epithelial ovarian cancer cells. (2016)
  • Author(s): Yoshikawa N, Kajiyama H, Nakamura K, Utsumi F, Niimi K, Mitsui H, Sekiya R, Suzuki S, Shibata K, Callen D, Kikkawa F.
  • Journal Title: Oncol Rep Volume: 35(5) Issue: 5 Pages: 2543-52
  • DOI: 10.3892/or.2016.4653
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of prognoses according to non-positive and positive spectrin αII expression detected immunohistochemically in epithelial ovarian carcinoma: a retrospective study. (2016)
  • Author(s): Maeda O, Miyata-Takata T, Shibata K, Kajiyama H, Mizuno M, Tamakoshi K, Shimoyama Y, Nakamura S, Kikkawa F.
  • Journal Title: Cancer Med Volume: in press Issue: 6 Pages: 1081-1092
  • DOI: 10.1002/cam4.683
  • Peer Reviewed / Open Access
• [Journal Article] Variable susceptibility of ovarian cancer cells to non-thermal plasma-activated medium. (2016)
  • Author(s): Utsumi F, Kajiyama H, Nakamura K, Tanaka H, Mizuno M, Toyokuni S, Hori M, Kikkawa F.
  • Journal Title: Oncol Rep. Volume: in press Issue: 6 Pages: 3169-3177
  • DOI: 10.3892/or.2016.4726
  • Peer Reviewed / Open Access
• [Journal Article] HOXB13 and ALX4 induce SLUG expression for the promotion of EMT and cell invasion in ovarian cancer cells. (2015)
  • Author(s): Yuan H, Kajiyama H, Ito S, Chen D, Shibata K, Hamaguchi M, Kikkawa F, Senga T.
  • Journal Title: Oncotarget. Volume: 30 Pages: 13359-70
  • Peer Reviewed / Open Access