Table 1.

Participation of exosomes in lung cancer metastasis

Source of exosome	Exosomal component	Mechanism or pathway	Principal effects	References
BMSCs	miR-210-3p, miR-193a-3p, and miR-5100	Exosome-mediated transfer of miRNAs activates STAT3 pathway	Enhanced cancer cell invasion and EMT	[86]
Melanoma	RAB1A, RAB5B, RAB7, and RAB27A	Reprogrammed cells were positive for c-Kit, receptor tyrosine kinase Tie2, and Met	Increased metastatic behavior, induced vascular leakiness at pre-metastatic sites, and reprogrammed bone marrow progenitor cells	[53]
Tumor	snRNAs	Activation of lung epithelial TLR3 to recruit neutrophils	TLR3-deficient mice showed reduced lung metastasis	[49]
		Phosphorylation of NF-κB p65 subunit and MAPKs ERK, JNK, and p38 signaling pathway	Exosomal snRNAs activated TLR3 to induce chemokine secretion and neutrophil recruitment
hucMSCs	–	Activation of Smad2/3, AKT/GSK-3β/β-catenin, NF-κB, ERK, JNK, and p38 MAPK in TGF-β1 signaling pathways	Promoted EMT, invasion, and migration, yet inhibited proliferation and promoted apoptosis of lung cancer cells	[84]
Lung tumor	circSATB2	Positive regulation of FSCN1 expression via miR-326 in lung cancer cells	Enhanced proliferation, migration, and invasion of NSCLC cells, as well as an induced abnormal proliferation of normal human bronchial epithelial cells	[66]
Lung tumor	miR-660-5p	miR-660-5p targeting of KLF9 to promote tumorigenesis	Enhanced proliferation, migration, viability, and metastasis	[67]
Lung tumor	circ-CPA4 and let-7 miRNA	CPA4-regulated effects via let-7 miRNA/PD-L1 axis	Promoted cell stemness, mobility, and drug resistance of NSCLC	[68]
Lung tumor	lnc-MMP2-2	TGF-β-mediated exosomal miRNA regulation	Increased cancer cell migration, invasion potential, and vascular permeability	[69]
Mouse and human lung tumor	integrins α6β4 and α6β1	Activation of Src phosphorylation and pro-inflammatory S100 gene expression	Associated with lung metastasis and predict organ-specific metastasis	[50]
SCLC patients and mouse model	miR-141	Activation of miR-141/KLF12 pathway	SCLC angiogenesis	[42]
Administration of lung cancer-derived exosomes to NIH/3T3 cells	miR-210	Modulation of JAK2/STAT3 signaling pathway and TET2 in recipient fibroblasts	Increased angiogenesis via elevated expression of proangiogenic factors MMP9, FGF2 and VEGFA	[43]
NSCLC cells	miR-619-5p	Targeted inhibition of RCAN1.4	Promoted growth and metastasis of NSCLCs	[73]
Adipocytes	MMP3 and MMP9	Transfer of MMP3 to activate MMP9	Promoted lung tumor metastasis	[85]
Plasma	Three clusters of miRNAs including miR-574-5p, 328-3p and miR-423-3p	Regulation of the Wnt/β-catenin pathway	Involved in preconditioning the metastatic niche and promoting bone metastasis of lung cancer	[78]