TY - JOUR
T1 - Wnt5a in cancer-associated fibroblasts promotes colorectal cancer progression
AU - Hirashima, Tomoaki
AU - Karasawa, Hideaki
AU - Aizawa, Takashi
AU - Suzuki, Takashi
AU - Yamamura, Akihiro
AU - Suzuki, Hideyuki
AU - Kajiwara, Taiki
AU - Musha, Hiroaki
AU - Funayama, Ryo
AU - Shirota, Matsuyuki
AU - Ohnuma, Shinobu
AU - Nakayama, Keiko
AU - Unno, Michiaki
N1 - Funding Information:
We are grateful to Enago ( www.enago ) for editorial work in the preparation of this manuscript. This work was supported by JSPS KAKENHI Grant Numbers JP19K09188 .
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/9/3
Y1 - 2021/9/3
N2 - Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and have been shown to promote cancer aggressiveness. In our previous study, analysis of expression profiles obtained from paired CAFs and normal fibroblasts from colorectal cancer (CRC) tissue revealed that gene sets related to the Wnt signaling pathway were highly enriched in colorectal CAFs. Furthermore, among the components of the β-catenin-independent Wnt pathway, Wnt5a was highly expressed in CAFs. Since Wnt5a is considered to be a regulator of CRC progression in CAFs, we performed immunohistochemical analysis on Wnt5a in 171 patients who underwent surgery for CRC. Positive staining for Wnt5a was often found in cancer stroma, particularly in fibromatous areas, although the immunoreactivity for Wnt5a was weak in cancer cells. Wnt5a status in CAFs was significantly associated with tumor size, depth of invasion, lymphatic and vascular invasion, lymph node metastasis, TNM stage, and recurrence. Subsequent in vitro analyses using human recombinant Wnt5a protein revealed that cancer cell proliferation and migration were significantly increased by stimulation with Wnt5a. Our findings suggest that Wnt5a-derived CAFs play a crucial role in CRC progression and have potential as a target of anti-cancer therapies.
AB - Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and have been shown to promote cancer aggressiveness. In our previous study, analysis of expression profiles obtained from paired CAFs and normal fibroblasts from colorectal cancer (CRC) tissue revealed that gene sets related to the Wnt signaling pathway were highly enriched in colorectal CAFs. Furthermore, among the components of the β-catenin-independent Wnt pathway, Wnt5a was highly expressed in CAFs. Since Wnt5a is considered to be a regulator of CRC progression in CAFs, we performed immunohistochemical analysis on Wnt5a in 171 patients who underwent surgery for CRC. Positive staining for Wnt5a was often found in cancer stroma, particularly in fibromatous areas, although the immunoreactivity for Wnt5a was weak in cancer cells. Wnt5a status in CAFs was significantly associated with tumor size, depth of invasion, lymphatic and vascular invasion, lymph node metastasis, TNM stage, and recurrence. Subsequent in vitro analyses using human recombinant Wnt5a protein revealed that cancer cell proliferation and migration were significantly increased by stimulation with Wnt5a. Our findings suggest that Wnt5a-derived CAFs play a crucial role in CRC progression and have potential as a target of anti-cancer therapies.
KW - Cancer-associated fibroblast
KW - Colorectal cancer
KW - Tumor microenvironment
KW - Wnt5a
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U2 - 10.1016/j.bbrc.2021.06.062
DO - 10.1016/j.bbrc.2021.06.062
M3 - Article
C2 - 34175688
AN - SCOPUS:85109403851
VL - 568
SP - 37
EP - 42
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
ER -