Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: A possible role for tumor progression

To examine the expression of the stromal cell-derived Factor 1 (SDF-1)/CXCR 4 receptor ligand system in pancreatic cancer cells and endothelial cells, we performed immunohistochemical analysis for 52 pancreatic cancer tissue s amples with anti-CXCR4 antibody and reverse transcription-PCR analysis for CXCR4 and SDF-1 in five pancreatic cancer cell lines (AsPC-1, BxPC-3, CFPAC -1, HPAC, and PANC-1), an endothelial cell line (HUVEC), and eight pancreat ic cancer tissues. We then performed cell migration assay on AsPC-1 cells, HUVECs, and CFPAC-1 cells in the presence of SDF-1 or MRC-9 fibroblast cell s. Immunoreactive CXCR4 was found mainly in pancreatic cancer cells and end othelial cells of relatively large vessels around a tumorous lesion. The im munopositive ratio in the pancreatic cancer was 71.2%. There was no statist ically significant correlation with clinicopathological features. SDF-1 mRN A expressions were detected in all pancreatic cancer tissues but not in pan creatic cancer cell lines and HUVECs; meanwhile, CXCR4 mRNA was detected in all pancreatic cancer tissues, cancer cell lines, and HUVECs. The results indicate that the paracrine mechanism is involved in the SDF-1/CXCR4 recept or ligand system in pancreatic cancer. In vitro studies demonstrated that S DF-1 significantly increased the migration ability of AsPC-1 and HUVECs, an d these effects were inhibited by CXCR4 antagonist T22, and that the cocult ure system with MRC-9 also increased the migration ability of CFPAC-1 cells , and this effect was significantly inhibited by T22. Our results suggested that the SDF-1/CXCR4 receptor ligand system may have a possible role in th e pancreatic cancer progression through tumor cell migration and angiogenes is.