Table 1.

Interaction of mesenchymal stem cells (MSCs) and osteosarcoma cells (OS).

OS Signal	Effect on MSCs	MSC Signal	Effect on OS	Reference
		Exosomes	Increase in COLGALT2 and proliferation.	Wang et al. 2020 [28]
		CM 1/co-culture	Increase in MMP2/9; STAT3 activation. Increased proliferation, invasion, and metastasis.	Wang et al. 2017 [29]
IL-8 (co-culture)	Increased IL-8.	IL-8 (co-culture)	Increased IL-8. Increased metastatic potential.	Kawano et al. 2018 [30]
		IL-6 CM/co-culture	Increase in MMP2/9; JAK2/STAT3 activation. Increased proliferation, migration, and doxorubicin resistance.	Lu et al. 2021 [31]
MCP-1, GRO-α, and TGFβ	Mesenchymal-to-amoeboid transition. Increase in MCP-1, GRO-α, IL-6, and IL-8 in the tumor environment.		Increased migration, invasion, and trans-endothelial migration.	Pietrovito et al. 2018 [20]
OS-EVs	LINE-1 hypomethylation increased VEGF-A.			Mannerström et al. 2019 [24]
		CM	STAT3 activation. Promote survival and drug resistance.	Tu et al. 2016 [25]
		MSC-EVs (under stress)	Increased migration. Apoptosis resistance.	Vallabhaneni et al. 2016 [32]
Co-culture	Increased TGFβ.	Co-culture IL-6	Increased OS proliferation, stemness & migration.	Cortini et al. 2016 [26]
		IL-6	STAT3 activation. Increased proliferation and metastasis.	Tu et al. 2012 [33]
CM/TGFβ	Increased IL-6, VEGF. Inhibit osteogenic differentiation.			Tu et al. 2014 [34]
		IL-8	CXCR1/Akt activation. Promotes metastasis.	Du et al. 2018 [35]
EVs/TGFβ	Increased IL-6.	Tumor-educated MSC	Activation of STAT3 signaling.	Baglio et al. 2017 [23]
		EVs	Cell growth under hypoxia. Activation of PI3K/AKT & HIF-1α.	Lin et al. 2019 [36]
		EVs	Activation of Hedgehog signaling. Tumor growth.	Qi et al. 2017 [37]

¹ CD, conditioned medium.