Abstract 1517: Pancreatic stellate cells and chemoresistant pancreatic cancer cells induce EMT gene expression in normal pancreatic ductal cells.

Abstract

Abstract Pancreatic cancer, one of the deadliest of human cancers, is associated with a collagen-rich pronounced stromal reaction. Previously, we showed that the collagen microenvironment increased the motility of human pancreatic ductal epithelial (HPDE) cells (Ottaviano AJ et al, Cancer Research 2006). Since stellate cells are one of the major contributors to the stromal reaction, we examined the effect of stellate cells on HPDE cells. HPDE cells were labeled with cell tracking dye and then co-cultured stellate cells to allow intimate cell-cell contact. HPDE cells were then isolated 72 hours later using FACS and changes in gene expression analyzed by real time PCR. We found that HPDE cells upregulated expression of epithelial-mesenchymal transition (EMT) markers Zeb1, Snail and vimentin. Stellate cells also increased expression of these EMT markers in HPDE cells expression Kras (HPDE-Kras). However, no change in these EMT markers were seen when the HPDE and stellate cells were prevented from direct cell-cell contact using transwell co-culture system. Treatment with TGF-b type I receptor inhibitor SB431542 blocked the effect of stellate cells on HPDE gene expression. Since ductal cells also encounter malignant cells in vivo, we also examined the effect of co-culture of ductal cells with cancer cells. HPDE cells failed to upregulate EMT markers when they were co-cultured with HPAFII/CD18 cell. However, when HPDE cells were co-cultured with chemo-resistant CD18 cells (CD18-CR), HPDE cells upregulated EMT markers. The effect of CD18-CR cells on HPDE gene expression was only observed when there was intimate cell-cell contact. Also, treatment with SB431542 blocked the effect on HPDE gene expression. These results indicate that the tumor microenvironment may affect the behavior of peri-tumoral non-malignant cells and thereby contribute to tumor progression. Citation Format: Krishan Kumar, Vaibhav Sahai, Kazumi Ebine, Hidayatullah G. Munshi. Pancreatic stellate cells and chemoresistant pancreatic cancer cells induce EMT gene expression in normal pancreatic ductal cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1517. doi:10.1158/1538-7445.AM2013-1517