Table 3.
The effects and mechanisms of CAFs on HCC cells/CCA cells
| HCC-CAFs | CCA-CAFs | |||
|---|---|---|---|---|
| Mediator | Effects and mechanisms in HCC | Mediator | Effects and mechanisms in CCA | |
| chemoresistance | HGF | CAF-derived HGF enhances the resistance of HCC cells to sorafenib and cisplatin by upregulating the expression of CD73 [18] | PIGF | Antagonizing CAF-secreted PIGF can alleviate chemoresistance effects [141] |
| CAFs-supernatants | CAF supernatant induces RCN1 expression in HCC cells, thereby enhancing resistance to sorafenib via the IRE1α-XBP1s pathway [48] | IGF2 | CAFs-secreted IGF2 stimulated IR/IGF1R signaling activation in erlotinib-resistant CCA cells [143] | |
| IL6 | CAF-secreted IL6 attenuates the sensitivity of CCA cells to chemotherapeutic drugs by inhibiting autophagy in CCA cells [146] | |||
| Cancer stemness | IL6 | CAFs-secreted HGF and IL6 enhanced stemness of CD24 + HCC cells through activated STAT3 pathway [57] | IL6 | CD146-positive vascular CAFs (vCAFs)-secreted IL6 enhanced the stemness of CCA [47] |
| HGF | CAFs-derived HGF enhanced stemness via (ERK)1/2–FRA1–HEY1 pathway [51] | MDSCs | CAFs indirectly regulated tumor stemness by recruiting MDSCs in the TME of CCA [90] | |
| HGF induces KRT19 expression in HCC cells via the MET-ERK1/2-AP1 and SP1 axis, thereby promoting stemness maintenance [54] | ||||
| FSTL1 | CAFs-derived FSTL1 promoted the stemness through the AKT/mTOR/4EBP1 signaling pathways [60] | |||
| CLCF1 | CAF-secreted CLCF1 enhances stemness by promoting the secretion of CXCL6 and TGF in HCC cells [61] | |||
| FOXQ1 | CAF promotes HCC initiation via the FOXQ1/NDRG1 axis [63] | |||
| RvD1 | RvD1 inhibits CAF-secreted COMP to antagonize the stemness effect via FPR2/ROS/FOXM1 signaling [69] | |||
| angiogenesis | VEGF | CAFs-derived VEGF promote the angiogenesis via EZH2 /VASH1 pathway [94] | VEGF | VEGF secreted by CAFs promoted the chemotaxis and assembly of lymphatic endothelial cells [161] |
| PIGF | CD90 positive CAFs have a strong correlation with PIGF expression in HCC tissues [96] | PIGF | PIGF produced by CAFs could compress the tumor vessel and deteriorate the hypoxic state in CCA [141] | |
| TGF-β and SDF1 | CAFs-derived TGF-β and SDF1 facilitated VM formation [97] | |||
| prolargin | CAFs-secreted prolargin inhibited the angiogenesis of HCC [45] | |||
| SPARCL1 | SPARCL1-positive fibroblasts could maintain the self-stabilization of blood vessels [41] | |||