Inspection about the influence of circulating tumor microenvironment for metastasis

2018 Fiscal Year Final Research Report

• 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
• 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

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.

Free Research Field

消化器癌

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。