Inspection about the influence of circulating tumor microenvironment for metastasis

• Project/Area Number: 16K10500
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Okayama University
• Principal Investigator: Shirakawa YAsuhiro 岡山大学, 医歯薬学総合研究科, 准教授 (60379774)
• Co-Investigator(Kenkyū-buntansha): 野間 和広 岡山大学, 大学病院, 助教 (10534761)
• Research Collaborator: KASHIMA hajime
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 癌関連線維芽細胞 / がん微小環境 / 食道癌 / リンパ節転移 / 浸潤能 / 遊走能 / 癌関連線維芽細胞尾 / 腫瘍微小環境 / 遠隔転移 / 転移

Outline of Final Research Achievements

Cancer-associated fibroblasts (CAFs) play a central role in the TME and have been reported to provide suitable conditions for the progression of esophageal cancer, similar to their role in other malignancies. We used clinical samples of esophageal cancer to reveal that CAFs promote lymph node metastasis and subsequently verified the intercellular relationships in vitro and in vivo using an orthotopic metastatic mouse model. In the analysis of clinical samples, FAP+ CAFs were strongly associated with lymph node metastasis rather than with other prognostic factors. Furthermore, CAFs affected the ability of esophageal cancer cells to acquire metastatic phenotypes in vitro; this finding was confirmed by data from an in vivo orthotopic metastatic mouse model showing that the number of lymph node metastases increased upon injection of co-cultured cancer cells and CAFs.

Academic Significance and Societal Importance of the Research Achievements

腫瘍微小環境において、CAFsは癌悪性化の中心的役割を果たすと考えられている。本研究ではCAFsの蓄積が食道扁平上皮癌のリンパ節転移を促進することを示唆している。 CAFsを標的とした治療は、将来の食道癌患者の転移を減らし、予後を改善することが期待できる。

Research Products

• [Journal Article] Cancer-associated fibroblasts (CAFs) promote the lymph node metastasis of esophageal squamous cell carcinoma. (2019)
  • Author(s): Kashima H, Noma K, Ohara T, Kato T, Katsura Y, Komoto S, Sato H, Katsube R, Ninomiya T, Tazawa H, Shirakawa Y, Fujiwara T.
  • Journal Title: International Journal of Cancer Volume: 144 Issue: 4 Pages: 828-840
  • DOI: 10.1002/ijc.31953
  • Peer Reviewed
• [Presentation] 癌関連線維芽細胞は食道癌のリンパ節転移を促進するか ～臨床検体の解析と同所移植モデルを用いた検証～ (2017)
  • Author(s): 賀島 肇，野間 和広，佐藤 浩明，桂 佑貴，加藤 卓也，大原 利章，田澤 大，白川 靖博，藤原 俊義
  • Organizer: 第 26 回日本がん転移学会学術集会・総会
• [Presentation] Cancer associated fibroblasts promote tumor metastasis coexisting with cancer cells in blood circulation (2017)
  • Author(s): Kashima H, Noma K, Sato H, Katsura Y, Kato T, Ohara T, Tazawa H, Shirakawa Y, Fujiwara T
  • Organizer: AACR annual meeting 2017
  • Int'l Joint Research
• [Presentation] 食道癌において癌関連線維芽細胞が 腫瘍転移に及ぼす影響の検証 (2016)
  • Author(s): 賀島 肇
  • Organizer: 第75回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] 癌関連線維芽細胞が食道癌の浸潤と転移に及ぼす影響の検証 (2016)
  • Author(s): 賀島 肇
  • Organizer: 第27回日本消化器癌発生学会総会
  • Place of Presentation: 鹿児島
  • Year and Date: 2016-09-15
• [Presentation] Correlation of FAP (fibroblast activation protein) expressing cancer associated fibroblasts (CAFs) and tumor metastasis in esophageal carcinoma. (2016)
  • Author(s): 賀島 肇
  • Organizer: AACR annual meeting 2016
  • Place of Presentation: New Orleans
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Remarks] 岡山大学医歯薬学総合研究科 消化器外科学 プロジェクト紹介
  • URL: http://www.ges-okayama-u.com/research.html