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《Journal of Third Military Medical University》 2018-01
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Glutamine synthetase from adipocytes inhibits peritoneal metastasis and angiogenesis of colon cancer in mice

CHEN Xiaozhen;LI Yifei;ZHANG Xuan;MIAO Hongming;LIANG Houjie;Department of Oncology,Southwest Hospital,Third Military Medical University;  
Objective To determine the effect of glutamine synthetase(GS) derived from adipocytes on intraperitoneal metastasis and angiogenesis of colon cancer. Methods Wide type(WT) and transgenetic mice(TgGS) were firstly identified with Western blotting for the expression level of GS protein in the adipocytes. Then mouse model of peritoneal metastasis of colon cancer MC38 cells was established by intraperitoneally injecting 2. 0 × 106 cells in the WT mice and TgGSmice. Then the cell implantation and tumor formation were observed. Immunohistochemical assay was used to detect the angiogenesis of the tumor mass.The fat tissues were harvested from WT and TgGSmice,and then the adipocytes were isolated and cultured to obtain the 2 kinds of adipocyte conditional media. Then tube formation assay,CCK8 assay,and Transwell chamber test were used to determine the effects of the 2 kinds of conditioned media on the tube formation,proliferation and migration in human umbilical vein endothelial cells(HUVECs). Results Western blotting showed that the expression level of GS protein in the adipocytes of TgGSmice was significantly increased than that in WT mice(P 0. 05). In the xenograft model,there were notably less(6. 33 ± 4. 04 vs 16. 00 ± 6. 56,P 0. 05) and smaller(2. 35 ± 1. 93 vs 9. 37 ± 5. 07,P 0. 01) tumors in the TgGSmice when compared with the WT mice. Immunohistochemical assay showed that the angiogenesis in TgGSmice were obviously less than that in WT mice(P 0. 05). The tube formation assay indicated that the total lengths of tubules was significantly shorter in the HUVECs co-cultured with adipocyte conditional medium from the TgGSmice than those with the medium from the WT mice group(P 0. 05). CCK8 assay displayed that there was no significant difference in the cell proliferation of HUVECs between the 2 kinds of media(P 0. 05). Transwell chamber test showed that there were less migrated cells in the HUVECs with TgGSculture medium than those with WT culture medium(15. 33 ± 5. 50 vs 78. 33 ± 13. 58,P 0. 01). Conclusion Adipocyte GS can inhibits peritoneal metastasis and tumor angiogenesis of colon cancer.
【Fund】: 国家自然科学基金青年科学基金(81702929)~~
【CateGory Index】: R735.35
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