Knockout of THBS1 gene improves immune microenvironment of visceral fat and inhibits intraperitoneal implantation and metastasis of colorectal cancer in mice

Abstract

Objective To investigate the effects of thrombospondin1 (THBS1) gene knockout on immune microenvironment and tumor progression of colorectal cancer. Methods THBS1 gene knockout (THBS1-/-) mice were constructed and its genotypes were determined by PCR and agarose gel electrophoresis. Subcutaneous tumor bearing and intraperitoneal implantation metastasis models of colorectal cancer were constructed in wild type (WT) and THBS1-/- mice to observe the effect of THBS1 on tumor growth. Immune cells in epididymal adipose of tumor bearing mice of both types were detected by flow cytometry. Results Compared with the WT mice, THBS1-/- mice showed no difference in tumor growth in colorectal cancer subcutaneous tumor bearing model (P>0.05), but significantly inhibited tumor growth in intraperitoneal implantation metastasis model (P 0.05). The proportions of MDSC and ly6C subgroup were not changed (P>0.05), while that of ly6G subgroup were decreased (P 0.05). Conclusion THBS1 gene knockout inhibits the intraperitoneal metastasis of colorectal cancer cells by enhancing tumor immunity.

Keywords

• thrombospondin-1
• colorectal cancer
• immune microenvironment
• epididymal fat