Table 1 The effect of MSC-derived mediators on tumor growth
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 | [40, 92,93,94,95,96, 103,104,105, 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, 127,128,129, 135,136,137] |
| 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, 142,143,144] |
| 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 | [152,153,154, 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, 173,174,175] |
| 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, 184,185,186,187,188] |
| 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] |