TY - JOUR
T1 - Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer
AU - Nishina, Takashi
AU - Deguchi, Yutaka
AU - Ohshima, Daisuke
AU - Takeda, Wakami
AU - Ohtsuka, Masato
AU - Shichino, Shigeyuki
AU - Ueha, Satoshi
AU - Yamazaki, Soh
AU - Kawauchi, Mika
AU - Nakamura, Eri
AU - Nishiyama, Chiharu
AU - Kojima, Yuko
AU - Adachi-Akahane, Satomi
AU - Hasegawa, Mizuho
AU - Nakayama, Mizuho
AU - Oshima, Masanobu
AU - Yagita, Hideo
AU - Shibuya, Kazutoshi
AU - Mikami, Tetuo
AU - Inohara, Naohiro
AU - Matsushima, Kouji
AU - Tada, Norihiro
AU - Nakano, Hiroyasu
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Interleukin (IL)-11 is a member of the IL-6 family of cytokines and is involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generate Il11 reporter mice. IL-11+ cells appear in the colon in murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuates the development of colitis-associated colorectal cancer. IL-11+ cells express fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11 induces the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis reveals that the expression of genes enriched in IL-11+ fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11+ fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment.
AB - Interleukin (IL)-11 is a member of the IL-6 family of cytokines and is involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generate Il11 reporter mice. IL-11+ cells appear in the colon in murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuates the development of colitis-associated colorectal cancer. IL-11+ cells express fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11 induces the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis reveals that the expression of genes enriched in IL-11+ fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11+ fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment.
UR - http://www.scopus.com/inward/record.url?scp=85104487657&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-22450-3
DO - 10.1038/s41467-021-22450-3
M3 - Article
C2 - 33863879
AN - SCOPUS:85104487657
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2281
ER -