Nishimura Satoko, Uno Makiko, Kaneta Yasuyuki, Fukuchi Keisuke, Nishigohri Haruyuki, Hasegawa Jun, Komori Hironobu, Takeda Shigeki, Enomoto Katsuhiko, Nara Futoshi, Agatsuma Toshinori
Biologics Research Laboratories, Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo, Japan.
PLoS One. 2012;7(6):e38618. doi: 10.1371/journal.pone.0038618. Epub 2012 Jun 8.
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.
为阐明与 MAS 相关的 G 蛋白偶联受体成员 D(MRGD)在癌症中的功能,我们使用稳定表达 MRGD 的小鼠成纤维细胞系 NIH3T3 研究了 MRGD 在体外和体内的致癌功能。我们还分析了 MRGD 在临床样本中的表达模式。我们发现,NIH3T3 中 MRGD 的过表达诱导了集落形成和多细胞球状体形成,并促进了裸鼠体内肿瘤的生长。换句话说,NIH3T3 中 MRGD 的过表达导致了接触抑制丧失、不依赖贴壁生长和体内肿瘤发生。此外,我们发现 MRGD 的配体β-丙氨酸增强了表达 MRGD 的 NIH3T3 细胞中的球状体形成。通过对临床癌症组织的研究,我们通过免疫组织化学以及实时 PCR 发现 MRGD 在几种肺癌中高表达。基于这些结果,MRGD 可能参与肿瘤发生,并且也可能是一个新的抗癌药物靶点。