Table 2.

Different mechanisms of pro- and anti-tumorigenic CAFs activities with the secretion associated.

Activity	Mechanisms	Proteins involved	Ref.
Proliferation, Survival	Stimulation of proliferation	TGF-β1, CXCL-12, FGF, POSTN, OPN, HGF, IL-6, IL-22	[83,84,85,86,87,88,89,90]
	Inhibition of apoptosis	Upregulation of BCL-2 and MCL1, downregulation of Bax	[83,84]
Chemoresistance	Inhibition of apoptosis	IL-6, IL-17A, PDGF, IGF, upregulation of MCL-1	[91,92,93,94,95]
	Stimulation of CSCs	C5a, IL-6	[72,94]
	Inhibition of bioavailability, vascular collapse	HA, collagen	[96,97,98,99]
	Ferroptosis, cell cycle inhibition	miR-522, CmiR-98-5p	[100,101]
Migration, Invasion, Metastasis	Stimulation of EMT	TGF-β, IL-32, PDGF, FGF, HGF, C3a	[102,103,104,105]
	Stimulation of cytoskeleton (motility)	TGF-β, upregulation of ARHGAP29	[103,106]
	ECM remodeling	MMP2, MMP3, MMP9	[59,104]
Angiogenesis	Recruitment/Proliferation of ECs and pericytes	VEGF, PDGF, CXCL-12, HGF, IL-6, IL-8	[107,108,109,110,111]
	Vascular mimicry	TGF-β, CXCL-12, MMP2	[112,113]
Immunomodulation	Recruitment/Proliferation of immune cells	IL-1β, CCL22, CXCL-12, CCL2, CXCL1, CXCL5, IL-8, PGE2	[80,114,115]
	Polarization of immune cells	IL-10, IL-12	[116,117,118,119,120]
	Immunotolerance (MDSC, Treg…)	CCL17, CCL22, CCL2, CXCL-12, IL-6, IL-17, IL-10, PD-1, CTLA4	[68,70,71,80,81,82]
	Inhibition of cytotoxic cells (lymphocyte, NK cells…)	TGF-β, CXCL1, IL-10, βig-h3, IL-6, IL-17	[68,70,121,122,123,124,125]
	Antigen presenting	MHC-II, CD74	[64,67,71]
Anti-tumorigenic	Inhibition of proliferation	IL-6, TNF-α, TGF-β	[126,127,128,129,130,131]
	Inhibition of CSCs stimulation	BMP4	[132]
	Inhibition of angiogenesis	Downregulation of HGF, FGF, VEGF, IL-8	[126,127,133]
	Inhibition of Treg cells	Downregulation of HGF, IL-6, FGF, CXCL-12	[126,127,133]