Abstract 1501: Direct interaction between human pancreatic cancer stem cells and stromal cells remodels extracellular matrix formation for cancer stem cell niche

Abstract Human pancreatic ductal adenocarcinomas consist of highly heterogeneous tumor cells that form tumor microenvironment cooperatively with stromal cells. Pancreatic cancer stem cells are reported to play important roles in chemotherapy and radiotherapy resistance. However, little is known about the microenvironment of pancreatic cancer stem cells. To investigate the microenvironment of pancreatic cancer stem cells with stromal cells, we isolated and characterized a novel subpopulation of pancreatic cancer stem cells, tentatively named KMC cells, from seven disseminated pancreatic ductal adenocarcinoma patients. KMC cells required direct cell-cell contacts to stromal cells for their clonogenic growth. KMC cells had self-renewal capacity and in vivo tumorigenicity. In vitro experiments demonstrated that stromal cells induced extracellular matrix (ECM) formation with thin filament structures and KMC cells changed the thin filament structures to basic lamina-like thick and bundled filament structures where laminin proteins were enriched. Moreover, KMC cells induced mRNA expression of laminin-5α and collagen type-IV in stromal cells, major components of basic lamina, but reduced mRNA expression of collagen type-I, collagen type-III, and fibronectin-I in stromal cells, major components of ECM. Our findings demonstrated that pancreatic cancer stem cells have the potential to form their microenvironment with basic lamina-like structures cooperatively with stromal cells, suggesting that targeting KMC cells and KMC cell-induced basic lamina-like structures in cancer therapy may improve prognosis of disseminated pancreatic ductal adenocarcinoma patients. 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 1501. doi:1538-7445.AM2012-1501