Abstract A196: Stromal cells suppress cancer development by secreted GAPDH-E-cadherin interaction

The cancer tissue contains lots of stromal cells. Among them, fibroblast-like stromal cellsregulate the growth of cancer cellspositively and negatively through secreted factors and adhesion. We have been studying the interactions between cancer cellsand stromal cellsusing small molecules that can modulate the interactions. We previously reported that gastric stromal cellsenhance the growth of gastric cancer cellsthrough secretion of IL-6, which is stimulated by gastric cancer cellsthrough PGE2 and TNF-alpha reciprocally. Here we report that GAPDH, a house keeping protein, is a negative regulator of the interactions. By purifying the growth inhibitory activity against gastric cancer cellsfrom secreted factors of gastric stromal cellwe unexpectedly identified GAPDH as an active substance. While GAPDH is known to be secreted extracellularly, its growth inhibitory activity has not yet. As a result, GAPDH is found to be secreted from various organ-derived stromal cellsand to inhibit the growth of various cancer celllines. We have found that this growth inhibitory activity of GAPDH doesn9t need its original enzymatic activity and GAPDH inhibits mTOR- p70S6 kinasepathway by binding to E-cadherin on cancer cellmembranes. We propose that negative regulation of cancer growth using GAPDH could be a new anti-cancer strategy. Citation Format: Kawada Manabu, Junjiro Yoshida, Hiroyuki Inoue, Shun-ichi Ohba, Manabu Yamasaki, Ihomi Usami, Shuichi Sakamoto, Hikaru Abe, Takumi Watanabe, Akio Nomoto, Masakatsu Shibasaki. Stromal cellssuppress cancer development by secreted GAPDH-E-cadherin interaction. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A196.