Elucidation of metastatic mechanism of breast cancer cells by the extravascular platelet aggregation and new therapeutic development

• Project/Area Number: 26461943
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kanazawa University
• Principal Investigator: INOKUCHI MASAFUMI 金沢大学, 附属病院, 助教 (90401918)
• Co-Investigator(Kenkyū-buntansha): 田島 秀浩 金沢大学, 附属病院, 講師 (00436825) ; 宮下 知治 金沢大学, 附属病院, 助教 (30397210)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 血小板 / 乳癌 / 化学療法抵抗性 / 上皮間葉転換 / 上皮-間葉転換

Outline of Final Research Achievements

We investigated the presence of platelets around breast cancer primary tumor cells, and the associations among platelets, tumor cells, chemoresistance, and epithelial-mesenchymal transition (EMT). We retrospectively analyzed data from patients with breast cancer who underwent neo-adjuvant chemotherapy. The presence of platelets(CD42b) was observed in 59% breast cancer biopsy pecimens. Platelet positive tumor cells showed EMT-like morphological changes and EMT marker expression. Primary tumor cells associated with platelets were less esponsive to neo-adjuvant chemotherapy. Platelets were an independent predictor of the response to chemotherapy upon multivariable analysis. In conclusion, platelets surrounding primary tumor cells were significantly associated with the chemotherapeutic response in breast cancer, and it may represent novel predictors of chemotherapeutic responses.

Research Products

• [Journal Article] Platelets surrounding primary tumor cells are related to chemoresistance. (2016)
  • Author(s): Ishikawa S, Miyashita T, Inokuchi M, Itas u Ninomiya, A. Karim Ahmed, John W. Harman, Sachio Fushida and Tetsuo Ohta
  • Journal Title: Oncol Rep. Volume: 36(2) Issue: 2 Pages: 787-794
  • DOI: 10.3892/or.2016.4898
  • Peer Reviewed
• [Presentation] 乳癌原発巣における血小板の役割：EMT誘導と化学療法抵抗性 (2015)
  • Author(s): 石川聡子、井口雅史、宮下知治、林 泰寛、尾山勝信、中川原寿俊、田島秀浩、高村博之、二宮 致、伏田幸夫、太田哲生
  • Organizer: 第３７回日本癌局所療法研究会
  • Place of Presentation: 幕張メッセ国際会議場(千葉県千葉市)
  • Year and Date: 2015-07-10
• [Presentation] Platelet predominant breast cancer is a new predictor for pathological complete response to neoadjuvant chemotherapy (2014)
  • Author(s): Satoko Ishikawa, Masafumi Inokuchi, Tomoharu Miyashita, Hidehiro Tajima, Hiroyuki Takamura, Itasu Ninomiya, Sachio Fushida, Tetsuo Ohta
  • Organizer: Sanantonio breast cancer symposium 2014
  • Place of Presentation: Henry B. Gonzalez Convention Center (San Antonio, Texas, USA)
  • Year and Date: 2014-12-09 – 2014-12-13
• [Presentation] 血小板がEMT を誘導し乳癌原発巣の化学療法抵抗性と関連する (2014)
  • Author(s): 石川聡子、井口雅史、宮下知治、田島秀浩、高村博之、二宮 致、伏田幸夫、藤村 隆、太田哲生
  • Organizer: 第22回日本乳癌学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2014-07-10 – 2014-07-12
• [Presentation] Tumor cells surrounded by platelets showed EMT and chemoresistance in primary breast cancer. (2014)
  • Author(s): 石川聡子、井口雅史、宮下知治、田島秀浩、高村博之、二宮 致、伏田幸夫、藤村 隆、太田哲生
  • Organizer: 第23回日本がん転移学会学術集会
  • Place of Presentation: 金沢市文化ホール（石川県金沢市）
  • Year and Date: 2014-07-10 – 2014-07-11