Carbonic anhydrase XII mediates the survival and prometastatic functions of macrophages in human hepatocellular carcinoma.

ABSTRACT: Macrophages constitute a major immune component in tumor tissues, but how these cells adapt to and survive in the nutrient-depleted and lactic acid-induced acidic tumor microenvironments is not yet fully understood. Here, we found that levels of carbonic anhydrase XII (CA12) expression were significantly and selectively upregulated on macrophages in human hepatocellular carcinoma (HCC). Transient glycolytic activation of peritumoral monocytes induced sustained expression of CA12 on tumor-infiltrating macrophages via autocrine cytokines and HIF1α pathways. On the one hand, CA12 mediated the survival of macrophages in relatively acidic tumor microenvironments, while on the other hand, it induced macrophage production of large amounts of C-C motif chemokine ligand 8 (CCL8), which enhanced can

SUBMITTER: Ning WR 

PROVIDER: S-EPMC8970669 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature