Circulating mitochondrial DNA promotes M2 polarization of tumor associated macrophages and HCC resistance to sorafenib.

ABSTRACT: Mitochondrial damage-associated molecular patterns (DAMPs) including mitochondrial DNA (mtDNA), TFAM (transcription factor A, mitochondrial), and ATP, which play crucial roles in the regulation of inflammatory environment in human diseases. However, the role of mitochondrial DAMPs in regulating tumor microenvironment (TME) remains unclear. Herein, we demonstrate that infiltration of M2-type tumor-associated macrophages (TAMs) was correlated with the resistance of hepatocellular carcinoma (HCC) to sorafenib. We found that cell-free mtDNA in the plasma was significantly increased in sorafenib-resistant HCC mice. Sorafenib induced mitochondrial dysfunction and promoted the release of mtDNA into extracellular matrix of HCC. Macrophages retook the mtDNA in the TME of HCC, activated TLR9 signali

SUBMITTER: Yang Q 

PROVIDER: S-EPMC11880550 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature