From: Mesenchymal stem cells as a double-edged sword in tumor growth: focusing on MSC-derived cytokines
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 | |
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 | |
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 | |
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 | |
Correlation of MSCs with cancer stem cells | BMP, IL-6, IL-8, CXCL6, and CXCL5 | Proliferation of CSCs and increasing their invasive properties | |
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 | |
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 | |
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 |