セミナー情報

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. Based on the function of MrgD, a large chemical library was screened in order to obtain MRGPRD antagonists to utilize in exploring the character. The obtained antagonists in turn inhibited the spheroid proliferation that is dependent on MRGPRD signaling.
From investigation of clinical cancer tissues, we found high expression of MRGD in several lung cancers by immunohistochemistry as well as real time PCR. These results are suggesting that MRGD could be involved in tumorigenesis and the antagonists could be new anti-cancer drugs targeting MrgD dependent oncogenic pathway.