The Expression of Formyl Peptide Receptor 1 is Correlated with Tumor Invasion of Human Colorectal Cancer.
The Expression of Formyl Peptide Receptor 1 is Correlated with Tumor Invasion of Human Colorectal Cancer.
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甲酰基肽受体1的表达与人结直肠癌肿瘤侵袭相关
DOI：
10.1038/s41598-017-06368-9
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发表时间：
2017-07-19
影响因子：
4.6
通讯作者：
Ye RD
中科院分区：
文献类型：
--
作者：
Li SQ;Su N;Gong P;Zhang HB;Liu J;Wang D;Sun YP;Zhang Y;Qian F;Zhao B;Yu Y;Ye RD
甲酰肽受体(FPR)是一种G蛋白偶联的趋化受体，主要表达于吞噬细胞。在多种肿瘤中也检测到FPRs的高表达，但FPR1在肿瘤侵袭和转移中的作用尚不清楚。在本研究中，我们研究了FPR在原发性结直肠癌(CRC)中的表达，并分析了FPR的表达与临床病理参数的关系。结直肠肿瘤组织中FPRs的表达水平显著高于远端正常组织和癌旁组织，尤其是FPR1的表达水平。FPR1mRNA的表达也与肿瘤浆膜浸润有关。FPR1蛋白在大肠上皮细胞和肿瘤浸润性中性粒细胞/巨噬细胞中均有表达。此外，利用结直肠癌细胞系SW480和HT29研究了FPR1在肿瘤侵袭和组织修复中的作用。与细胞膜FPR1表达较低的HT29细胞相比，SW480细胞表面FPR1的高表达与显著增加的迁移有关。最后，在结肠炎相关性结直肠癌小鼠模型中，pr1基因缺失提高了由此产生的基因敲除小鼠的存活率，与野生型小鼠相比。我们的数据表明，FPR1可能在结直肠癌患者的肿瘤细胞侵袭中发挥重要作用。
Formyl peptide receptors (FPRs) are G protein-coupled chemoattractant receptors expressed mainly in phagocytic leukocytes. High expression of FPRs has also been detected in several cancers but the functions of FPR1 in tumor invasion and metastasis is poorly understood. In this study, we investigated the expression of FPRs in primary human colorectal cancer (CRC) and analyzed the association of FPRs expression with clinicopathological parameters. The levels of FPRs mRNA, especially those of FPR1, were significantly higher in colorectal tumors than in distant normal tissues and adjacent non-tumor tissues. FPR1 mRNA expression was also associated with tumor serosal infiltration. FPR1 protein expression was both in the colorectal epitheliums and tumor infiltrating neutrophils/macrophages. Furthermore, the functions of FPR1 in tumor invasion and tissue repair were investigated using the CRC cell lines SW480 and HT29. Higher cell surface expression of FPR1 is associated with significantly increased migration in SW480 cells compared with HT29 cells that have less FPR1 membrane expression. Finally, genetic deletion offpr1increased the survival rate of the resulting knockout mice compared with wild type littermates in a mouse model of colitis-associated colorectal cancer. Our data demonstrate that FPR1 may play an important role in tumor cell invasion in CRC patients.
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影响因子：
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