Exosomes in the tumor microenvironment of sarcoma: from biological functions to clinical applications

Ye, Huali; Hu, Xin; Wen, Yang; Tu, Chongqi; Hornicek, Francis; Duan, Zhenfeng; Min, Li

doi:10.1186/s12951-022-01609-0

Journal of Nanobiotechnology

Table 1 Effect of sarcoma-derived exosomes on the TME cells

From: Exosomes in the tumor microenvironment of sarcoma: from biological functions to clinical applications

Sarcoma type	TME cells	Exosomal cargos	Mechanisms	Clinical significance	References
OS	Macrophages	Tim-3	Induce conversion to M2 macrophages	Pre-metastatic lung formation↑	[40]
LPS	Macrophages	miR-25-3p, miR-92a-3p	Increase IL-6 secretion via TLR7/8-dependent pathway	Progression↑	[41]
OS	Osteoclasts; endothelial cells	miR-21-5p, miR-148a-3p	Promote bone remodeling; enhance angiogenesis	Metastasis↑	[42]
OS	Osteoblasts; osteoclasts; endothelial cells	\	Promote bone remodeling; facilitate angiogenesis via VEGF/ANGPT2/FGF2-mediated mechanism	Progression and metastasis↑	[43]
OS	Monocytes	miR-501-3p	Promote bone remodeling via PTEN/PI3K/Akt pathway	Metastasis↑	[45]
OS	Osteoclasts	miR-146a-5p	Promote bone remodeling via IkBa/NF-kB pathway	Metastasis↑	[46]
OS, FS	Monocytes	\	Transform the monocyte phenotype to inhibit CD4+ T cells	Immune suppression↑	[49]
OS	Macrophages	\	Induce conversion to M2 macrophages	Immune suppression↑	[50]
OS	Macrophages	Rab22a-NeoF1, PYK2	Activate RhoA and STAT-3	Pre-metastatic lung formation↑	[14]
EWS	CD33+ and CD14+ cells	\	Impede dendritic cell differentiation and maturation	Immune suppression↑	[55]
OS	CD11b+ Gr-1+ cells	\	Induce CD11b+ cells infiltration to lung	Pre-metastatic lung formation↑	[56]
OS	MSCs	\	Induce MSCs phenotypic conversion	Progression and metastasis↑	[58]
OS	MSCs	\	Induce LINE-1 hypomethylations for MSCs transformation	Progression and metastasis↑	[59]
MFS	Fibroblasts	miR-1260b	Decrease PCDH9 level	Progression and Infiltration↑	[67]
OS	Fibroblasts	\	Induce fibroblast phenotypic conversion	Progression↑	[68]
OS	Fibroblasts	TGF-β1	Induce myofibroblast/CAFs differentiation	Pre-metastatic lung formation↑	[70]
OS	Endothelial cells; OS cells	EWSAT1	Promote angiogenesis; regulate Akt and Erk signaling via EWSAT1/miR-326/KRas ceRNA mechanism	Progression↑	[73]

OS, osteosarcoma; miR, microRNA; LPS, liposarcoma; TLR7/8, toll-like receptor 7 and 8; VEGF, vascular endothelial growth factor; ANGPT2, angiopoietin 2; FGF2, fibroblast growth factor 2; PTEN, phosphatase and tensin homologue deleted on chromosome 10; PI3K, phosphoinositide 3 kinase; Akt, AKT8 virus oncogene cellular homolog; IkBa, inhibitor of NF-κB alpha; NF-κB, nuclear factor kappa B; FS, fibrosarcoma; RhoA, Ras homolog gene family, member A; STAT-3, signal transducer and activator of transcription 3; EWS, Ewing’s sarcoma; MSCs, mesenchymal stem cells; LINE-1, long interspersed element; MFS, myxofibrosarcoma; PCDH9, protocadherin 9; CAFs, cancer-associated fibroblasts; EWSAT1, Ewing sarcoma associated transcript 1; Erk, extracellular signal-regulated kinase; KRas, v-Ki-ras2Kirsten rat sarcoma viral oncogene homolog; ceRNA, competing endogenous RNA

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