Fig. 2

Heterogeneous cellular origins of CAFs. CAFs in the HCC microenvironment may be derived from HCC cells, HSCs, MSCs, and HSECs. Hypoxia and TGF-β can induce EMT and expression of α-SMA and FAP in HCC cells. HSCs can differentiate into CAFs under stimulation with CM or exosomal miRNA-21 secreted by HCC cells. CM generated from HCC cells can also induce the expression of tenascin-C and SDF-1 in MSCs. HSECs are a potential cellular origin of CAFs in the HCC microenvironment