Cancer‐associated fibroblasts secrete Wnt2 to promote cancer progression in colorectal cancer

Recent studies have shown that the tumor microenvironment plays a significant role in the progression of solid tumors. As an abundant component of the tumor microenvironment, cancer‐associated fibroblasts (CAFs) have been shown to promote tumorigenesis and cancer aggressiveness, but their molecular...

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Veröffentlicht in:Cancer medicine (Malden, MA) MA), 2019-10, Vol.8 (14), p.6370-6382
Hauptverfasser: Aizawa, Takashi, Karasawa, Hideaki, Funayama, Ryo, Shirota, Matsuyuki, Suzuki, Takashi, Maeda, Shimpei, Suzuki, Hideyuki, Yamamura, Akihiro, Naitoh, Takeshi, Nakayama, Keiko, Unno, Michiaki
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Sprache:eng
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Zusammenfassung:Recent studies have shown that the tumor microenvironment plays a significant role in the progression of solid tumors. As an abundant component of the tumor microenvironment, cancer‐associated fibroblasts (CAFs) have been shown to promote tumorigenesis and cancer aggressiveness, but their molecular characteristics remain poorly understood. In the present study, paired CAFs and normal fibroblasts (NFs) were isolated from five colorectal cancer (CRC) tissues from patients who underwent surgical resection. The gene expression profiles of CAFs and NFs identified by RNA sequencing were compared to understand the complex role of CAFs in cancer progression. Gene Set Enrichment Analysis revealed that the gene sets related to the Wnt signaling pathway were highly enriched in CAFs, as well as TGFβ signaling, which is considered to be a regulator of CAFs. Among the components of this pathway, Wnt2 was specifically expressed. The observations led us to speculate that Wnt2 is extremely involved in regulating CRC progression by CAFs. Thus, we performed immunohistochemical analysis on Wnt2 in 171 patients who underwent surgery for colorectal adenocarcinoma. Positive staining for Wnt2 was mainly observed in cancer stroma, although the immunoreactivity was weak in cancer cells. Wnt2 expression in CAFs was significantly correlated with depth of tumor (P 
ISSN:2045-7634
2045-7634
DOI:10.1002/cam4.2523