Mouse forestomach carcinoma cells immunosuppress macrophages through             transforming growth factor-β1.
Peritoneal implantation metastasis of gastric cancer cells is associated             with poor prognosis. Peritoneal macrophages are the most important immune cells             in the abdominal cavity to control tumor metastasis. In the present study, the             immunosuppressive effects of mouse forestomach cells on macrophages were examined.             Conditioned medium from mouse forestomach cell cultures were used to treat isolated             peritoneal macrophages. A colorimetry-based phagocytosis assay was performed to             investigate the functional change of macrophages. The alteration of cytokine secretion             by macrophages was measured by ELISA assay. Specific markers of macrophage polarization             were analyzed by real-time RT-PCR. TGF-β1 signaling was evaluated by western blotting.             Neutralization experiments were performed using an anti-TGF-β1 antibody. Conditioned             medium reduced the phagocytotic capability of macrophages. Lower TNF-α and IL-1β             levels and higher IL-10 and VEGF levels were observed. Real-time RT-PCR showed             increased mRNA levels of M2 macrophage markers. Further study revealed that TGF-β1             was significantly elevated in the conditioned medium and TGF-β1 signaling was             activated in the macrophages by the treatment of conditioned medium. Neutralization             of TGF-β1 reversed the immunosuppressive effects on macrophages. Immunosuppressive             macrophages can be induced by conditioned medium from mouse forestomach cell cultures.             These effects appeared to occur through the production of TGF-β1 by the tumor             cells. Targeted TGF-β1 intervention may help to control peritoneal metastasis             of gastric cancers.
General Surgery Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
Huaxing
H
Luo
Yingxue
Y
Hao
Bo
B
Tang
Dongzhu
D
Zeng
Yan
Y
Shi
Peiwu
P
Yu
D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D007165:Immunosuppression Therapy; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010537:Peritoneum / Q000166:cytology*; D010587:Phagocytosis; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D017077:Culture Media, Conditioned; D053773:Transforming Growth Factor beta1