Study on the effects and mechanisms of M2 macrophages on PYCR1-promoted biological behavior of hepatocellular carcinoma cells

Abstract In this study, we aimed to investigate the effects of PYCR1 and M2-type macrophages on the malignant behaviors of hepatocellular carcinoma (HCC) cells and determine the mechanisms underlying these effects. We induced M2 polarization of macrophages by treating THP-1 cells with interleukin-4 (IL-4) and interleukin-13 (IL-13) and cultured HCC cells with medium conditioned using these macrophages. This co-culture promoted cancer cell invasion, migration, and epithelial–mesenchymal transition, whereas knockdown of pyrroline-5-carboxylic acid reductase 1 (PYCR1) suppressed these malignant behaviors, as well as inhibiting cell proliferation. We further observed that co-culture with M2 macrophage-conditioned medium suppressed apoptosis and ferroptosis of HCC cells; again, PYCR1 knockdown reversed these alterations. In summary, conditioned medium derived from M2 macrophages mediates PYCR1-induced cell proliferation, apoptosis inhibition, and ferroptosis suppression in HCC, ultimately promoting progression of HCC through various signaling pathways. These results indicate the potential of PYCR1 as a therapeutic target for treatment of liver cancer.