Abstract 40: Targeting MLCK expression in cancer-associated fibroblasts disrupts tumor-stromal interactions in gastric cancer

Abstract

Abstract Aim: Accumulating evidence has indicated that microenvironment consisting of stromal affects cancer progression. However, the mechanism by which cancer cells and fibroblasts, the major cell type in stromal, interact with each other during tumor development remains to be elucidated. Our aim is to identify the molecular mechanism involved in tumor-stromal cell interactions in human gastric cancer. Methods: The expression of Myosin Light Chain Kinase (MLCK) in gastric cancer-associated fibroblasts (CAF) was detected by quantitative RT-PCR. The effects of CAF, which was interfered with MLCK, on cell proliferation, apoptosis, migration and invasion in vitro were measured. Results: Primary fibroblast cultures were established from human gastric cancer. MLCK was upregulated in CAF compared with NF (fibroblasts from patient matching non-cancerous tissues). Small interfering RNA knockdown of MLCK in CAF impaired the augmenting effect of CAF on gastric cancer cell proliferation, and induced the apoptosis of gastric cancer cells (9.1+0.8 vs 22.3+1.4, p<0.05). Moreover, the ability of stimulating gastric cancer cells migration (77.7+4.3 vs 61+4.2, p<0.05) and invasion (60.9+1.5 vs 48.3+1.4, p<0.05) in vitro by CAF was also inhibited when MLCK was knocked down. Furthermore, gastric cancer cells can also activate CAF in a MLCK-dependent manner. Conclusions: These findings indicate that MLCK mediates the cross-talk between tumor and stromal in gastric cancer, and suggest that targeting stromal cells for MLCK interference may be a therapeutic target in human gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 40. doi:1538-7445.AM2012-40