M1-like tumor-associated macrophages promote colorectal cancer progression through feedback activation of the IL1β/NF-κB signaling activity.

Tumor-associated macrophages (TAMs) are the main tumor infiltrating immune cell types in tumor microenvironment (TME) that have related to tumor progression. However, crosstalk between TAMs and colorectal cancer (CRC) cells remains poorly understood. In this study, conditioned media (CM) was harvested from CRC cells or activated TAMs. Immunofluorescence assay and real-time quantitative PCR were used to detect phenotypic alteration of macrophages. Scratch test, colony-formation assay, and transwell invasion assay were performed to measure the migration and invasion of CRC. Enzyme-linked immunosorbent assay, and bioinformatics analysis were used to investigate the underlying mechanisms. Moreover, an in vivo model was applied to validate the effects of TAMs on CRC progression. Our findings showed that THP-1-derived macrophages exhibited an M1-like TAMs characteristics after culturing with CM from CRC cells. CM from activated M1-like TAMs promoted the colony forming, invasion, and migration abilities of CRC cells by secreting IL1β. TAMs-derived IL1β promoted CRC progression via activating the NF-κB signaling pathway, which in turn increased the production of CCL2 that induced macrophage recruitment. Neutralization of IL1β or CCL2 disrupted this loop and inhibited TAMs-mediated tumor progression and macrophage migration. In summary, our data indicates that CM from CRC could polarize macrophages into M1-like TAMs. And these TAMs promoted CRC migration and invasion through activating IL1β/NF-κB signaling, which in turn enhanced to the secretion of CCL2 that promoted macrophage recruitment, indicating a crosstalk between TAMs and tumor cells in CRC microenvironment.