P2X7R promotes angiogenesis and tumor-associated macrophage recruitment by regulating the NF-κB signaling pathway in colorectal cancer cells

Abstract

Background Overexpression of P2 × 7R has been observed in several tumors and is related to cancer advancement and metastasis. However, the role of P2 × 7R in colorectal cancer (CRC) patients is not well understood. Methods In the current study, overexpression of P2 × 7R and the effects at the molecular and functional levels in CRC were assessed in a mouse orthotopic model. Functional assays, such as the CCK-8 assay, wound healing and transwell assay, were used to determine the biological role of P2 × 7R in CRC cells. CSC-related genes and properties were detected via sphere formation and real-time PCR assays. The underlying mechanisms were explored by Western blotting, real-time PCR and Flow cytometry. Results In this study, we found that overexpression of P2 × 7R increase in the in vivo growth of tumors. P2 × 7R overexpression also increased CD31, VEGF and concurrent angiogenesis. P2 × 7R upregulates aldehyde dehydrogenase-1 (ALDH1) and CSC characteristics. Transplanted tumor cells with P2 × 7R overexpression stimulated cytokines to recruit TAMs to increase the growth of tumors. We also found that the NF-κB signaling pathway is involved in P2 × 7R-induced cytokine upregulation. Conclusion P2 × 7R promotes NF-κB-dependent cytokine induction, which leads to tumor-associated macrophage (TAM) recruitment to control tumor growth and advancement and remodeling of the stroma. Our findings demonstrate that P2 × 7R plays a key role in TAM recruitment, which may be a therapeutic target for CRC patients.