Pathogenic mechanism of hepatocellular carcinoma analyzed by single-cell transcriptomics combined with proteomics
Objective To explore novel mechanisms regulating the progression of hepatocellular carcinoma(HCC)and to provide new therapeutic strategies for HCC through single-cell transcriptomics,proteomics and in vivo and in vitro experiments.Methods We reanalyzed single-cell transcriptomic and proteomic data of HCC obtained from public database using R package.Key cell subpopulations that respond to the HCC microenvironment were identified.The regulatory effects of these cell subpopulations on the HCC progression were validated in mouse subcutaneous tumor-bearing model and in-vitro system.Results Bioinformatic analysis revealed that the interaction between macrophages and the extracellular matrix(ECM)in the HCC microenvironment was closely related to tumor progression.In vivo and in vitro experiments confirmed that the tumor-associated macrophages exhibited stronger interactions with collagens,a major component of the ECM,compared to non-tumor-infiltrating macrophages.In a tumor-bearing mouse model,injection of BAPN to depolymerize ECM inhibited tumor growth,reduced tumor stiffness,suppressed angiogenesis,and decreased infiltration of bone marrow-derived suppressive cells(P＜0.05).Conclusion The interaction between macrophages and ECM plays a critical role in regulating the HCC microenvironment.Targeting the tumor ECM may serve as a new strategy for the treatment of HCC.
万方数据
维普
