Surgical trauma contributes to progression of colon cancer by downregulating CXCL4 and recruiting MDSCs

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Abstract

Surgical stress has been shown to facilitate the tumor growth and metastasis of colon cancer. To unravel the mechanisms underlying surgery induced-colon cancer progression, a syngeneic transplantation tumor model was established with murine colon cancer CT26 cells and the effect of laparotomy on tumor progression was investigated. Especially the expression of several CXC chemokines was assayed, and its roles in regulating myeloid-derived suppressor cells (MDSCs) recruitment were analyzed. We found that laparotomy promoted in vivo tumor growth and angiogenesis. CXCL4 expression was significantly downregulated by laparotomy in the tumor tissue and the peritoneal cavity. Functionally, CXCL4 overexpression significantly reduces tumor volume compared to control. Through analysis of CD11b+/Gr1+ MDSCs cell, we found an upregulated proportion of MDSCs in the tumor tissues and peritoneal cavity following laparotomy, and this enhancement was blocked after CXCL4 overexpression. Further, a negative correlation was found between CXCL4 expression and MDSC amounts in clinical samples. Higher CXCL4 expression and lower MDSCs proportion is positively related to overall survival.

Conclusion

Surgical trauma contributes to colon cancer progression by downregulating CXCL4 and hence promoting MDSC recruitment, which leads to an immunosuppressive environment.

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