Gut microbiota-stimulated cathepsin K secretion mediates TLR4-dependent M2 macrophage polarization and promotes tumor metastasis in colorectal cancer

摘要

Imbalance of intestinal microbiota is associated with high CTSK expression and advanced progression of colorectal cancer. a Left panel: Immunohistochemistry (IHC) analysis of lipopolysaccharides (LPS) in colorectal cancer (CRC) tissues and adjacent non-tumor tissues. Right panel: IHC analysis of LPS in CRC tissues w/o metastasis. b Upper left panel: Sketch map shows the orthotopic implantation of MC38 cells in antibiotic-treated mice w/o intragastrical administration of E. coli. Upper right panel: HE staining shows the hepatic metastasis foci in antibiotic-treated mice w/o intragastrical administration of E. coli. The scatter diagram on the right represents the number of tumor nodules. Lower panel: The primary tumor developed by implantation of MC38 cells in antibiotic-treated mice w/o intragastrical administration of E. coli. c LPS expression in the primary tumors developed by implantation of MC38 cells in antibiotic-treated mice w/o intragastrical administration of E. coli. d Heat map depicting the differentially expressed genes in eight pairs of human non-metastatic and metastatic CRC tissues. Red and blue indicate high and low expression of genes. e Real-time PCR analysis shows the expression of differentially expressed genes in response to LPS treatment in SW480 and RKO cell lines. f Representative images of IHC staining analyses of CTSK and LPS in non-metastatic and metastatic CRC tissues. g Upper panel: Western blot analysis of CTSK in FHC, SW480 and RKO cell lines in response to LPS treatment. Lower panel: Western blot analysis of LPS releasing and CTSK in FHC, SW480, and RKO cells pretreated with E. coli