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

• The effect of different colon cancer cell lines on macrophages is evaluated.
• THP-1 cells with supernatant from the HT-29, HCT-15 or Colo205 line are co-cultured.
• Secreted colon cancer factors differentiate THP-1 into a mixed M1/M2 macrophage.
• Colon cancer supernatants enhance the phagocytic capacity and migration of THP-1.

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.