RESUMEN
Objective To investigate the effect of M2 macrophages resident in gastric cancer microenvironment on the tumor-promoting effect of human gastric cancer-derived mesenchymal stem cells (GC-MSCs).Methods Macrophages in BALB/c mice were depleted by using clodronate liposomes.The tumor volumes and weights in nude mice co-injected with GC-MSCs and BGC-823 with and without macrophage depletion were recorded.Tumor tissues of nude mice and gastric cancer patients were collected,and M2 macrophage-associated genes and proteins were detected by RT-PCR and western blot.Furthermore,the regulating effect of GC-MSCs on macrophage polarization to M2-subtype was validated in the co-culture experiment in vitro.Results Tumor growth in GC-MSCs co-injected mice was significantly inhibited by macrophage depletion (P=0.009).Results of RT-PCR and western blot showed that the transcription and expression of M2 macrophage-associated proteins were significantly higher in tumor tissues from GC-MSCs co-injected mice than those in the control group.Moreover,the transcription and expression levels of M2 macrophage-associated proteins were also high-er in gastric cancer tissues than those in the corresponding adjacent normal tissues.After co-culture with GC-MSCs directly,the expressions of M2 macrophage-associated proteins were significantly up-regulated in THP-1-derived macrophages.Conclusion M2 macrophages in gastric cancer microenvironment might play a critical role in the tumor-promoting effect of GC-MSCs.