CRMP4 Up-regulates M2 Macrophages and Myeloid-derived Suppressor Cells to Promote Pancreatic Cancer in Mice

Abstract

Background/Aim: We previously observed higher prevalence of high-grade pancreatic intraepithelial neoplasia (PanIN) in LSL-Kras^G12D/+; Pdx1^Cre/+ (KC-Crmp4^wild) mice than LSL-Kras^G12D/+; Pdx1^Cre/+; Crmp4^–/– (KC-Crmp4^–/–) mice. This study investigated the relationship between collapsin response mediator protein 4 (CRMP4) and immune cell infiltration in pancreatic cancer. Materials and Methods: PanIN was induced by intraperitoneal injection of caerulein into KC-Crmp4^wild and KC-Crmp4^–/– mice, and immune cells in PanIN lesions were compared. Subcutaneous tumors were created by injecting Pan02 cells, and tumor diameter was compared between Crmp4^wild and Crmp4^–/– mice every 7 days. Peritumoral immune cells were examined immunohisto chemically. Results: High-grade PanIN in KC mice showed statistically significantly high expression of CD163 (p=0.031) and CD11b (p=0.027). Following subcutaneous injection of Pan02 cells, tumor diameter was greater in Crmp4^wild mice than Crmp4^–/– mice. Crmp4^wild mice exhibited higher CD163 and CD11b expression than Crmp4^–/– mice in tumors (p<0.001). Conclusion: CRMP4 might promote pancreatic cancer by up-regulating M2 macrophages and myeloid-derived suppressor cells.