Abstract 4277: Comparative gene expression analysis of proliferating stromal cells from pancreatic ductal adenocarcinoma, pancreatitis and normal pancreas

Introduction: Stromal cells associated with cancer cells are considered an important component of tumor microenvironment of pancreatic cancer. The intratumoral desmoplasia characteristic of pancreatic cancer is a result of growing carcinoma paracrine action on surrounding normal tissue cells. Selective targeting of tumor stroma cells can markedly increase the effectiveness of currently used chemotherapeutic agents against pancreatic cancer. Therefore, a search for new targets in stromal cells is an important part of developing new combined therapies of this disease. Our work was aimed at comparative studying of gene expression in stromal cells of normal pancreas, pancreatitis and pancreatic ductal adenocarcinoma tissues. Methods: Cultured stromal cells were obtained from samples of normal pancreatic (n=3), pancreatitis (n=3) and ductal adenocarcinoma tissues (n=4). The cell cultures obtained were preliminary characterized by immunofluorescence, RT-PCR and western blotting. A full genome gene expression analysis was performed using a modified SAGE technique. Expression of selected dysregulated genes was analyzed by quantitative PCR. Results: Morphological and immunofluorescent analyses of the obtained primary stromal cultures indicated that they could be assigned to pancreatic stellate cells (PSC). The SAGE analysis allowed to quantitatively estimate expression of 9860 genes in normal PSC, 8744 PSC genes in pancreatitis, and 9311 genes in tumor PSC. A comparison of normal and tumor PSC revealed statistically significant (P