Wnt5a-induced M2 polarization of tumor-associated macrophages via IL-10 promotes colorectal cancer progression

• DOI: 10.1186/s12964-020-00557-2
• Publication Date: 2020-03-30T14:02:49Z
• Authors: Qing Liu; Chaogang Yang; Shuyi Wang; Dongdong Shi; Chen Wei; Jialin Song; Xiaobin Lin; Rongzhang Dou; Jian Bai; Zhenxian Xiang; Sihao Huang; Keshu Liu; Bin Xiong
• Keywords: WNT5A; CD68; CD163; Tumor progression; Macrophage polarization

Abstract Background Tumor-associated macrophages (TAMs) in the tumor microenvironment influence initiation, invasion and metastasis. Several studies have shown that Wnt5a is mainly expressed stroma, especially TAMs. However, whether regulates polarization biological function of TAMs colorectal cancer (CRC) incompletely understood. Methods Immunofluorescence staining was performed to detect CD68 expression tissues from patients (63 CRC specimens VS 20 normal tissues). RT-qPCR, flow cytometry, ELISA inhibitors were carried out explore role Clone formation transwell assays determine effects Wnt5a–treated on proliferation, migration vitro. Finally, a xenograft model applied confirm + tumorigenesis. Results We found high /CD68 ratio significantly associated with poor prognosis TAM an M2-like subtype. Subsequently, we induced secrete IL-10, which then acted as autocrine cytokine induce M2 these macrophages. IL-10 neutralizing antibody completely reversed pro-M2 effect Wnt5a. Mechanistically, CaKMII-ERK1/2-STAT3 pathway required for Wnt5a-mediated Furthermore, Wnt5a-induced promoted cells invasion; knockdown impaired pro-tumor functions Conclusions Our data indicate could by regulating pathway–mediated secretion, ultimately promoting growth metastasis CRC.