School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
School of Pharmacy, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Ruijin Road (No.2), Shanghai, 200025, China.
Sci Rep. 2017 Jul 19;7(1):5918. doi: 10.1038/s41598-017-06368-9.
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 of fpr1 increased 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.
甲酰肽受体(FPRs)是主要表达于吞噬白细胞的 G 蛋白偶联趋化性受体。在几种癌症中也检测到 FPRs 的高表达,但 FPR1 在肿瘤侵袭和转移中的功能知之甚少。在本研究中,我们研究了原发性人结直肠癌(CRC)中 FPRs 的表达,并分析了 FPRs 表达与临床病理参数的关系。FPRs mRNA 的水平,特别是 FPR1 的水平,在结直肠肿瘤中明显高于远处正常组织和相邻非肿瘤组织。FPR1 mRNA 表达也与肿瘤浆膜浸润有关。FPR1 蛋白表达既存在于结直肠上皮细胞中,也存在于肿瘤浸润的中性粒细胞/巨噬细胞中。此外,还使用 CRC 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 HT29 细胞相比,FPR1 膜表达较少的 SW480 细胞的表面表达更高,与细胞迁移显著增加相关。最后,在结肠炎相关性结直肠癌的小鼠模型中,与野生型同窝仔相比,fpr1 基因缺失导致的敲除小鼠的存活率增加。我们的数据表明,FPR1 可能在 CRC 患者的肿瘤细胞侵袭中发挥重要作用。