Tumor-associated macrophage-derived exosomes transmitting miR-193a-5p promote the progression of renal cell carcinoma via TIMP2-dependent vasculogenic mimicry.

ABSTRACT: Previous studies have investigated whether tumor-associated macrophages (TAMs) play tumorigenic and immunosuppressive roles to encourage cancer development, but the role of TAMs in regulating vasculogenic mimicry (VM) in clear-cell renal cell carcinoma (ccRCC) cells has not been completely clarified. We conducted immunostaining of the tumor-associated macrophage biomarkers CD68/CD163 and double staining for PAS/CD31 in ccRCC human specimens to find that higher TAM infiltration was positively correlated with VM formation. Then we demonstrated that TAM-derived exosomes downregulate TIMP2 expression in RCC cells to promote VM and invasion by shuttling miR-193a-5p. Mechanistic analysis indicated that HIF-1α upregulation in macrophages could transcriptionally increase miR-193a-5p expression. Ex

SUBMITTER: Liu Q 

PROVIDER: S-EPMC9021253 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature