Overexpressed decorin in pancreatic cancer: potential tumor growth inhibition and attenuation of chemotherapeutic action.

Abstract

The aim of this study was to investigate the expression and significance of decorin in pancreatic cancer. Decorin expression in normal pancreas and excised tumors was examined by real-time quantitative PCR, Western blot analysis, and immunohistochemistry. Reverse transcription-PCR was used to analyze cultures of pancreatic cancer and stellate cells. Growth-inhibitory effects of decorin in vitro were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test, Western blot, and fluorescence-activated cell-sorting analysis. Pancreatic cancer was characterized by striking overexpression of decorin mRNA in tumor tissues (9-fold by real-time quantitative PCR; 44 patients versus 18 healthy donors; P < 0.01). Strong decorin immunostaining was observed in the extracellular matrix of pancreatic cancer tissue, whereas tumor cells were devoid of decorin. Double staining for anti-smooth muscle actin and decorin and reverse transcription-PCR analysis of primary cultures revealed pancreatic stellate cells as the putative source of decorin. Human recombinant decorin was able to suppress growth of pancreatic cancer cells in vitro through p21 mediated G(1)-S block of the cell cycle. However, in contrast to the previously described chemotherapy-potentiating capacity of decorin, this proteoglycan attenuated the cytostatic action of carboplatin and gemcitabine toward pancreatic cancer cells. Decorin might exert an antiproliferative effect toward pancreatic cancer cells, thus playing a role in a host stromal reaction aimed at sequestering and inhibiting growing malignant cells. However, in clinical settings, the importance of collagen-associated decorin as a moderate antitumor modality would be undermined by its ability to attenuate the efficiency of chemotherapeutics. Considering the general failure of adjuvant therapies in pancreatic cancer, the role of decorin in this process warrants further investigation.