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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]