The role of tumor-associated neutrophils in endometrial cancer displaying tumor-related leukocytosis.

• Project/Area Number: 15H06378
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: Osaka University
• Principal Investigator: Matsumoto Yuri 大阪大学, 医学部附属病院, 助教 (90756488)
• Research Collaborator: Kuroda Hiromasa ; Kozasa Katsumi ; Yokoi Eriko ; Komura Naoko
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); 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)
• Keywords: 子宮体癌 / TRL / TAN / 浸潤・転移 / 前転移ニッチ / CD66b / G-CSF

Outline of Final Research Achievements

Objective: The aim of this study is to investigate the causative mechanism of poor prognosis in endometrial cancer patients displaying TRL (tumor-related leukocytosis), focusing on TAN (tumor-associated neutrophils).
Results and Conclusion: The TAN density of the patient`s endometrial cancer was significantly associated with pretreatment peripheral neutrophils and shorter progression-free-survival. Iv vitro and in vivo experiments revealed that TAN enhanced the invasive capacity and chemotactic activity of endometrial cancer. TAN was infiltrated in the premetastatic lungs and made premetastatic niche, expressing chemoattractant S100a8/9 that attracted the endometrial cancer cells of TRL model. These results indicate that TAN contribute to tumor cell metastases by premetastatic niche formation.

Research Products

• [Journal Article] Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma. (2017)
  • Author(s): Yokoi, E. Mabuchi, S. Takahashi, R. Matsumoto, Y. Kuroda, H. Kozasa, K. Kimura, T.
  • Journal Title: J Gynecol Oncol Volume: 28(2) Issue: 2
  • DOI: 10.3802/jgo.2017.28.e19
  • Peer Reviewed / Open Access
• [Journal Article] The prognosis of high-risk early-stage cervical cancer patients who did not receive standard postoperative concurrent chemoradiotherapy: a monoinstitutional study. (2017)
  • Author(s): Kuroda, H. Mabuchi, S. Matsumoto, Y. Kozasa, K. Sasano, T. Takahashi, R. Ueda, Y. Tomimatsu, T. Yoshino, K. Kimura, T.
  • Journal Title: Eur J Gynaecol Oncol Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Preclinical investigations of PM01183 (lurbinectedin) as a single agent or in combination with other anticancer agents for clear cell carcinoma of the ovary. (2016)
  • Author(s): Takahashi, R. Mabuchi, S. Kawano, M. Sasano, T. Matsumoto, Y. Kuroda, H. Kozasa, K. Hashimoto, K. Sawada, K. Kimura, T.
  • Journal Title: PLoS ONE Volume: 17;11(3)
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic significance of systemic neutrophil and leukocyte alterations in surgically treated endometrial cancer patients: a monoinstitutional study. (2015)
  • Author(s): Takahashi R, Mabuchi S, Kawano M, Sasano T, Matsumoto Y, Kuroda H, Hisamatsu T, Kozasa K, Sawada K, Hamasaki T, Kimura T.
  • Journal Title: Gynecol Oncol Volume: 137(1) Issue: 1 Pages: 112-8
  • DOI: 10.1016/j.ygyno.2015.02.006
  • Peer Reviewed / Open Access
• [Presentation] 骨髄由来免疫抑制細胞(MDSC)は子宮頸癌組織中の癌幹細胞を増加させる (2016)
  • Author(s): 黒田浩正 馬淵誠士 小笹勝巳 笹野智之 髙橋良子 松本有里 橋本香映 澤田健二郎 木村正
  • Organizer: 第58回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 米子
  • Year and Date: 2016-07-08
• [Presentation] The role of G-CSF-induced myeloid-derived suppressor cells （MDSC）in the induction of cancer stem-like cells in cervical cancer. (2016)
  • Author(s): Kuroda, H. Mabuchi, S. Kozasa, K. Sasano, T. Takahashi, R. Matsumoto, Y. Hashimoto, K. Sawada, K. Kimura, T.
  • Organizer: 第68回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-21
• [Presentation] 17β-estradiol promotes cervical cancer progression by stimulating the production of myeloid derived suppressor cells from hematopoietic stem cells. (2016)
  • Author(s): Kozasa, K. Mabuchi, S. Kuroda, H. Sasano, T. Takahashi, R. Matsumoto, Y. Hashimoto, K. Sawada, K. Kimura, T.
  • Organizer: 第68回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-21
• [Book] Management of Metastatic and Recurrent Cervical Cancer. (2016)
  • Author(s): Mabuchi, S. Kawano, M. Takahashi, R. Kuroda, H.
  • Publisher: Handbook of Gynecology, Springer
• [Book] Fertility-Sparing Treatment for Early-Stage Cervical Cancer. (2016)
  • Author(s): Kuroda, H. Mabuchi, S. Kozasa, K. Kimura, T.
  • Publisher: Handbook of Gynecology, Springer
• [Book] Cervical Cancer: General Overview. (2016)
  • Author(s): Mabuchi, S. Kawano, M. Matsumoto, Y. Kimura, T.
  • Publisher: Handbook of Gynecology, Springer
• [Book] Management of Early-Stage and Locally Advanced Cervical Cancer. (2016)
  • Author(s): Mabuchi, S. Kawano, M. Sasano, T. Kuroda, H.
  • Publisher: Handbook of Gynecology, Springer