P2X7R promotes angiogenesis and tumour‐associated macrophage recruitment by regulating the NF‐κB signalling pathway in colorectal cancer cells

• Published in: Journal of cellular and molecular medicine Vol. 24; no. 18; pp. 10830 - 10841
• Main Authors: Yang, Chunhui, Shi, Shuang, Su, Ying, Tong, Jing‐Shan, Li, Liangjun
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.09.2020; John Wiley and Sons Inc
• Subjects: Aldehyde dehydrogenase; Angiogenesis; Antibodies; Cancer; cancer stem cells; Cells; Cholecystokinin; Colorectal cancer; Colorectal carcinoma; Cytokines; Flow cytometry; Ligands; Macrophages; Medical prognosis; Metastases; NF-κB protein; NF‐κB; Original; P2X7R; Signal transduction; Stroma; TAMs; Therapeutic targets; Tumors; tumour growth; Vascular endothelial growth factor; Western blotting; Wound healing; St Louis Missouri; United States > US; NF-κB; cancer stem cells; TAMs; angiogenesis; P2X7R; tumour growth
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15708

Overexpression of P2X7R has been observed in several tumours and is related to cancer advancement and metastasis. However, the role of P2X7R in colorectal cancer (CRC) patients is not well understood. In the current study, overexpression of P2X7R 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 P2X7R 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. In this study, we found that overexpression of P2X7R increases in the in vivo growth of tumours. P2X7R overexpression also increased CD31, VEGF and concurrent angiogenesis. P2X7R up‐regulates aldehyde dehydrogenase‐1 (ALDH1) and CSC characteristics. Transplanted tumour cells with P2X7R overexpression stimulated cytokines to recruit tumour‐associated macrophage (TAMs) to increase the growth of tumours. We also found that the NF‐κB signalling pathway is involved in P2X7R‐induced cytokine up‐regulation. P2X7R promotes NF‐κB–dependent cytokine induction, which leads to TAM recruitment to control tumour growth and advancement and remodelling of the stroma. Our findings demonstrate that P2X7R plays a key role in TAM recruitment, which may be a therapeutic target for CRC patients.