MRGD, a MAS-related G-protein Coupled Receptor, Promotes Tumorigenisis and Is Highly Expressed in Lung Cancer

To elucidate the function of MAS-related GPCR, member D (MRGD) in cancers, we investigated the in vitro and in vivo oncogenic function of MRGD using murine fibroblast cell line NIH3T3 in which MRGD is stably expressed. The expression pattern of MRGD in clinical samples was also analyzed. We found that overexpression of MRGD in NIH3T3 induced focus formation and multi-cellular spheroid formation, and promoted tumors in nude mice. In other words, overexpression of MRGD in NIH3T3 induced the loss of contact inhibition, anchorage-independent growth and in vivo tumorigenesis. Furthermore, it was found that the ligand of MRGD, beta-alanine, enhanced spheroid formation in MRGD-expressing NIH3T3 cells. From investigation of clinical cancer tissues, we found high expression of MRGD in several lung cancers by immunohistochemistry as well as real time PCR. Based on these results, MRGD could be involved in tumorigenesis and could also be a novel anticancer drug target.为阐明MAS相关G蛋白偶联受体（MAS-related GPCR）成员D（MRGD）在癌症中的功能，本研究以稳定过表达MRGD的小鼠成纤维细胞系NIH3T3为模型，探究了MRGD的体外及体内致癌功能。同时分析了MRGD在临床样本中的表达模式。研究发现，在NIH3T3细胞中过表达MRGD可诱导灶集落形成与多细胞球状体形成，并可促进裸鼠体内肿瘤生成。换言之，NIH3T3细胞中MRGD过表达可引发接触抑制丧失、非锚定依赖性生长以及体内致瘤性。此外，本研究还发现MRGD的配体β-丙氨酸（beta-alanine）可增强表达MRGD的NIH3T3细胞的球状体形成能力。通过对临床癌症组织的检测，本研究通过免疫组化及实时荧光定量PCR（real-time PCR）技术，在多例肺癌组织中检测到MRGD的高表达。综上，MRGD可能参与肿瘤发生过程，同时亦可作为新型抗肿瘤药物靶点。