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P2X7R promotes angiogenesis and tumour-associated macrophage recruitment by regulating the NF-κB signalling pathway in colorectal cancer cells.
Journal of Cellular and Molecular Medicine ( IF 5.3 ) Pub Date : 2020-07-31 , DOI: 10.1111/jcmm.15708 Chunhui Yang 1 , Shuang Shi 1 , Ying Su 1 , Jing-Shan Tong 2 , Liangjun Li 1
Journal of Cellular and Molecular Medicine ( IF 5.3 ) Pub Date : 2020-07-31 , DOI: 10.1111/jcmm.15708 Chunhui Yang 1 , Shuang Shi 1 , Ying Su 1 , Jing-Shan Tong 2 , Liangjun Li 1
Affiliation
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.
中文翻译:
P2X7R通过调节结直肠癌细胞中的NF-κB信号通路来促进血管生成和与肿瘤相关的巨噬细胞募集。
在一些肿瘤中已经观察到P2X7R的过表达,并且与癌症的进展和转移有关。但是,P2X7R在大肠癌(CRC)患者中的作用尚不清楚。在当前的研究中,在小鼠原位模型中评估了P2X7R的过表达以及对CRC中分子和功能水平的影响。功能测定,例如CCK-8测定,伤口愈合和transwell测定,用于确定P2X7R在CRC细胞中的生物学作用。通过球体形成和实时PCR分析检测了CSC相关基因和特性。通过蛋白质印迹,实时PCR和流式细胞术探索了潜在的机制。在这项研究中,我们发现P2X7R的过表达在体内肿瘤生长中增加。P2X7R的过表达也增加了CD31,VEGF和同时发生的血管生成。P2X7R上调醛脱氢酶-1(ALDH1)和CSC特性。带有P2X7R过表达的移植肿瘤细胞刺激细胞因子募集肿瘤相关巨噬细胞(TAM),以增加肿瘤的生长。我们还发现NF-κB信号通路与P2X7R诱导的细胞因子上调有关。P2X7R促进依赖NF-κB的细胞因子诱导,从而导致TAM募集以控制肿瘤的生长以及基质的进展和重塑。我们的发现表明,P2X7R在TAM募集中起关键作用,这可能是CRC患者的治疗靶标。我们还发现NF-κB信号通路与P2X7R诱导的细胞因子上调有关。P2X7R促进依赖NF-κB的细胞因子诱导,从而导致TAM募集以控制肿瘤的生长以及基质的进展和重塑。我们的发现表明P2X7R在TAM募集中起关键作用,这可能是CRC患者的治疗靶标。我们还发现NF-κB信号通路与P2X7R诱导的细胞因子上调有关。P2X7R促进依赖NF-κB的细胞因子诱导,从而导致TAM募集以控制肿瘤的生长以及基质的进展和重塑。我们的发现表明P2X7R在TAM募集中起关键作用,这可能是CRC患者的治疗靶标。
更新日期:2020-09-28
中文翻译:
P2X7R通过调节结直肠癌细胞中的NF-κB信号通路来促进血管生成和与肿瘤相关的巨噬细胞募集。
在一些肿瘤中已经观察到P2X7R的过表达,并且与癌症的进展和转移有关。但是,P2X7R在大肠癌(CRC)患者中的作用尚不清楚。在当前的研究中,在小鼠原位模型中评估了P2X7R的过表达以及对CRC中分子和功能水平的影响。功能测定,例如CCK-8测定,伤口愈合和transwell测定,用于确定P2X7R在CRC细胞中的生物学作用。通过球体形成和实时PCR分析检测了CSC相关基因和特性。通过蛋白质印迹,实时PCR和流式细胞术探索了潜在的机制。在这项研究中,我们发现P2X7R的过表达在体内肿瘤生长中增加。P2X7R的过表达也增加了CD31,VEGF和同时发生的血管生成。P2X7R上调醛脱氢酶-1(ALDH1)和CSC特性。带有P2X7R过表达的移植肿瘤细胞刺激细胞因子募集肿瘤相关巨噬细胞(TAM),以增加肿瘤的生长。我们还发现NF-κB信号通路与P2X7R诱导的细胞因子上调有关。P2X7R促进依赖NF-κB的细胞因子诱导,从而导致TAM募集以控制肿瘤的生长以及基质的进展和重塑。我们的发现表明,P2X7R在TAM募集中起关键作用,这可能是CRC患者的治疗靶标。我们还发现NF-κB信号通路与P2X7R诱导的细胞因子上调有关。P2X7R促进依赖NF-κB的细胞因子诱导,从而导致TAM募集以控制肿瘤的生长以及基质的进展和重塑。我们的发现表明P2X7R在TAM募集中起关键作用,这可能是CRC患者的治疗靶标。我们还发现NF-κB信号通路与P2X7R诱导的细胞因子上调有关。P2X7R促进依赖NF-κB的细胞因子诱导,从而导致TAM募集以控制肿瘤的生长以及基质的进展和重塑。我们的发现表明P2X7R在TAM募集中起关键作用,这可能是CRC患者的治疗靶标。