IL-11 is a novel marker of stromal fibroblasts that promote tumors in a murine model of colitis-associated cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15626
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Toho University
• Principal Investigator: NISHINA Takashi 東邦大学, 医学部, 助教 (50598365)
• Research Collaborator: DEGUCHI Yutaka ; TAKEDA Wakami ; NAKANO Hiroyasu
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: レポーターマウス / 大腸癌 / IL-11 / サイトカイン / 間質細胞

Outline of Final Research Achievements

Interleukin (IL)-11 is a member of the IL-6 family of cytokines. Although IL-11 has been considered to promote the development of colitis-associated cancer in both human and mice, it is unclear which types of cells produce IL-11 under such conditions. To address this issue, we generated IL-11-EGFP reporter mice and characterized IL-11-producing cells by using colitis-associated cancer models and the mouse model for familial adenomatous polyposis. While EGFP-positive cells were absent in the colon of control IL-11-EGFP mice, large numbers of EGFP-positive cells appeared in the tumor of both murine tumor models in a kinase activity-dependent manner. Immunohistochemical and FACS analysis revealed that EGFP-positive cells were largely stromal fibroblasts, but not myofibroblasts. Moreover, in human colorectal cancer specimens, stromal fibroblasts produced IL-11 in the tumors. The increase of IL-11 production was positively correlated with the cancer progression.

Free Research Field

病態生化学

Academic Significance and Societal Importance of the Research Achievements

大腸癌の増悪には、癌細胞だけでなく、その周囲に存在する間質細胞が重要な役割を担っていることが示されつつあるが、不明な点も多い。今回の我々の結果から癌細胞周囲に存在する特異的な間質線維芽細胞がサイトカインのひとつであるIL-11を産生することで、癌形成に寄与していることを見出した。また、このIL-11の産生機構を阻害剤により抑制すると、癌細胞の増殖抑制や細胞死が認められた。すなわち、IL-11の産生誘導機構の解明は、大腸癌の新たな治療標的の創出につながる研究基盤になると考えられる。