Colorectal cancer cell-derived interleukin-6 enhances the phagocytic capacity and migration of THP-1 cells.

Macrophages perform a versatile range of functions in response to environmental stimuli. In the present study, we evaluated whether interleukin-6 (IL-6), a cytokine released from colorectal cancer (CRC) cells and associated with CRC pathogenesis and metastasis, modulates the phagocytic capacity and migratory ability of macrophages, using a monocyte-macrophage THP-1 cell model and human peripheral monocytes. We found that CRC cells enhanced the phagocytic capacity and migration of THP-1 cells and human peripheral monocytes. CRC cell culture supernatants and recombinant IL-6 neutralized with anti-IL-6 and anti-gp130 antibodies considerably decreased IL-6-mediated phagocytosis by and migration of THP-1 cells and human peripheral monocytes, via the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Our data suggest that CRC cells secreting IL-6 via STAT3 phosphorylation can enhance the phagocytic capacity and migration of macrophages in the tumor microenvironment.

Culture supernatants of different colon cancer cell lines induce specific phenotype switching and functional alteration of THP-1 cells.

We developed an in vitro model to evaluate the effect of products secreted from different colorectal cancer (CRC) cell lines on specific phenotypic switching and functional alterations in THP-1 cells. We co-cultured the human monocytic cell line, THP-1, or phorbol-12-myristate-13-acetate (PMA)-treated THP-1 cells, (THP-1p), with supernatants from either the HT-29 (Dukes' B), HCT-15 (Dukes' C), or Colo205 (Dukes' D) cell lines, and assessed the cells for macrophage differentiation. The surface marker and cytokine profiles suggested that secreted CRC factors differentiated THP-1 cells into a "mixed" M1/M2 phenotype, although HT-29 and Colo205 supernatants induced THP-1p cells into predominantly M1-like macrophages and M2-like macrophages, respectively. Further, all three CRC supernatants enhanced the phagocytic capacity and migration of THP-1 and THP-1p cells, altering their phenotype to a more M2-kind. Therefore, different CRC cell lines induced specific phenotype switching and functional polarization of THP-1 cells.