Effects of chemokine fractalkine and m2 macrophages on biological functions of pancreatic cancer cell line / 肿瘤

ABSTRACT

Objective: To investigate the effects of cytokine Fractalkine (FKN) combined with M2-type macrophages on the proliferation, invasion, and migration of human pancreatic cancer PANC-1 cells. Methods: The recombinant lentivirus HBLV-h-FKN-GFP-PURO carrying FKN gene was constructed and infected into PANC-1 cells. THP-1 cells, a kind of monocytes of human leukemia, were induced into M2-type macrophages by phorbol 12-myristate 13-acetate (PMA) and interleukin-4 (IL-4) in suquence. Then the non-contacting co-culture model of pancreatic cancer cells and M2-type macrophages with different expression level of FKN was established by Transwell chamber system. The proliferation, invasion and migration of human pancreatic cancer PANC-1 cells were detected by CCK-8 method, Transwell chamber test and wound-healing assay, respectievely. Results: As compared with the uninfected control and empty lentivirus infected groups, the expression level of FKN protein was significantly increased in human pancreatic cancer PANC-1 cells infected with recombinant lentivirus HBLV-h-FKN-GFP-PURO (both P < 0.001). THP-1 cells were successively induced to become M2-type macrophages with high expression of arginase-1 (Arg-1) and low expression of inducible nitric oxide synthase (iNOS) protein (PArg-1 < 0.001, PiNOS < 0.01). The recruiting ability of PANC-1 cells to M2 type macrophages was enhanced after FKN over-expression (P < 0.001). The proliferation, invasion and migration abilities of PANC-1 cells were increased after FKN over-expression (all P < 0.001), and were more significantly increased after co-culture with M2-type macrophages (all P < 0.01). There were interactions between M2-type macrophages and FKN for proliferation, invasion and migration abilities of PANC-1 cells (P < 0.01, P < 0.01, P < 0.05). Conclusion: The chemokine FKN promotes the recruitment of PANC-1 cells to M2-type macrophages. Both FKN and M2-type macrophages can enhance the proliferation, invasion and migration abilities of PANC-1 cells, and there is synergistical interaction between them.