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Promoting effect of granulocyte- macrophage colony stimulating factor on liver metastasis of colon cancer and its underlying mechanisms
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Abstract:
Objective: To investigate the effect of granulocyte-macrophage colony stimulating factor（GM-CSF）on liver metastasis of colon cancer and the underlying mechanisms. Methods: GM-CSF gene and shRNA targeting GM-CSF were stably transfected into human colon cancer HCT116 and SW480 cell lines, respectively; the expression of GM-CSF was detected by ELISA. Liver metastasis model of colon cancer was established by injecting cancer cells into spleen. Some of the model mice were intraperitoneally injected with recombinant human GM-CSF every other day (3 μg，0.6 μg/mice). Four weeks after model establishment，liver gross and tumor metastasis were observed. The expression of N-cadherin and matrix metalloproteinase 2 (MMP2) was detected by Real-time fluorescent quantitative PCR while E-cadherin was detected by Western blotting. Results: According the expression of GM-CSF, HCT116 cells were grouped into low, median and high expression subgroups (GMlo, GMint, GMhiHCT116); Meanwhile, GMKDSW480 group (GM-CSFknockdown) was established. Liver gross and pathological results showed that injecting of GM-CSF-overexpressed HCT116 cells or exogenous GM-CSF remarkably increased the amounts of liver metastasis; In contrast, knockdown of GM-CSF showed the opposite effect.Furthermore，GM-CSF over-expression significantly up-regulated the levels of N-cadherin and MMP2 as well as down-regulated the levels of E-cadherin (P<0.05). Conclusion: GM-CSF can potently promote liver metastasis of colon cancer xenograft, which may be due to the down-regulation of E-cadherin and up-regulation of N-cadherin and MMP2.
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Project Supported:
Project supported by the State Key Development Program for Basic Research of China（No. 2015CB553704），and the National Natural Science Foundation of China（No.81672803，81472647）
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