Table 1.

The effect of MSC-derived mediators on tumor growth

Pro-tumorigenic activity of MSCs	Factors secreted by	Effects of secreted factors and mediators	References
Immunosuppression	MSCs: TGFβ, IFNγ, TNFα, PGE2, CCL2, galectin-9, HGF, CTLA-4, soluble PD-L1 and PD-L2, NO, HLA-G, IDO, IL-1α, IL-1β, IL-4 and IL-6	Immune tolerance T, B, NK, Dendritic cell inhibition Promotion of Treg cells proliferation Recruitment of MDSCs Apoptosis of lymphocytes and neutrophils Reduction of CD80/CD86 expression on APCs	[40, 92–96, 103–105, 109]
Promotion of angiogenesis	VEGF, FGF-2, βFGF, PDGF, IL-6, IL-8, TGFβ and angiopoietin-1	Promotion of tumor angiogenesis Transformation into smooth muscle cells and pericytes Mobilization and recruitment of MSCs into neovascularization sites Tumor vessel formation Inducing expressing of junctional proteins	[51, 88, 123, 124, 127–129, 135–137]
Transition of mesenchymal stem cells to cancer-associated fibroblasts	CAFs: α-SMA, tenascin-C, fibroblast surface protein (FSP), CCL5, CXCL12, IL-6, IL-4, IL-8, TNF, TGFβ, VEGF	Stimulation of tumor growth Promotion of tumor vascularization	[88, 142–144]
Epithelial–mesenchymal transition (EMT)	HGF, EGF, PDGF, leptin and TGFβ	Induction of transcriptional regulators: snail, slug, twist, Zeb1 Increasing the metastatic capacity Inducing EMT and promoting a cancer stem cell (CSC) phenotype	[152–154, 157, 158]
Correlation of MSCs with cancer stem cells	BMP, IL-6, IL-8, CXCL6, and CXCL5	Proliferation of CSCs and increasing their invasive properties	[90, 164, 165]
Promotion of tumor metastasis	Lysyl oxidase (LOX), TGFβ, FGF, HGF, EGF, CCL5, CXCL5, CXCL1, CXCL7 and CXCL8	Promotion of tumor cell migration Extracellular matrix modulation Enhancing tumor cell invasiveness and inducing EMT Activation of matrix metalloproteinase 9 (MMP-9) Overexpression of rho-associated kinase	[59, 75, 167, 171, 173–175]
Inhibition of apoptosis in cancer cells	VEGF, FGF-2, PDGF, HGF, BDNF, SDF-1α, IGF-1 and IGF-2, TGF-β and IGFBP-2	Inhibition of tumor cell apoptosis and promotion of tumor proliferation Stimulation of the angiogenesis	[52, 184–188]
Promotion of drug resistance	CXCL12, EGF, IGF, IL-6, IL-7, IL-8 and PGE-2	Reducing caspase 3 activity Inhibition of apoptosis following cytotoxic therapy Promotion of the CSCs formation	[91, 133, 164, 196, 198]