TGF-β secreted by tumor-associated macrophages promotes proliferation and invasion of colorectal cancer via miR-34a-VEGF axis.

Tumor-associated macrophages (TAMs) were reported to be involved in colorectal cancer (CRC) progression. However, its biological role and underlying mechanism in CRC remained to be elucidated. In this study, the expressions of the macrophage marker CD68 and transforming growth factor β1 (TGF-β1) in CRC tumor tissues and adjacent tissues were detected by immunohistochemistry. The expression levels of miR-34a, TGF-β1 and vascular endothelial growth factor (VEGF) in CRC tumor tissues and peripheral blood macrophages were measured by quantitative real-time PCR (qRT-PCR) and western blot. TGF-β1 levels in culture supernatant were detected by ELISA. The cell proliferation and invasion of human CRC cell lines CL187 and HCT116 were determined by MTT assay and Transwell assay, respectively. The results showed that the expression of miR-34a was downregulated whereas TGF-β1 and VEGF were upregulated in CRC tumor tissues and peripheral blood macrophages. TGF-β1 secreted by TAMs promoted the proliferation and invasion of CRC cells. TGF-β1-mediated miR-34a downregulation contributed to the proliferation and invasion of CRC cells via upregulating VEGF. MiR-34a in vivo exerted anti-tumor effect in CRC via inhibiting VEGF expression. In conclusion, TGF-β1 secreted by TAMs promoted CRC proliferation and invasion through regulating miR-34a/VEGF axis.