Table 1.

Summary of recent studies regarding extracellular vesicle (EV)‐mediated organotropic metastasis

Metastatic sites	EV donor cells	EV cargo	EV recipient cells	Downstream effects	References
Lung	Breast cancer and melanoma cells	Integrin α6 β1 and integrin α6 β4	Surfactant protein C‐positive lung epithelial cells	Upregulation of pro‐inflammatory gene expression S100A4, A6, A10, A11, A13, and A16	Hoshino et al 51
	Breast cancer cells	miRNA‐125b	Pulmonary resident fibroblasts	Transformation of fibroblasts into activated phenotypes	Vu et al 52
	Metastatic breast cancer cells	miRNA‐105	Endothelial cells	Targeting tight junction protein zonula occludens‐1 (ZO‐1), hampering endothelial monolayers’ barrier functions, and increasing vascular permeability	Zhou et al 55
	Colorectal cancer cells	miRNA‐25‐3p	Endothelial cells	Targeting KLF2 and KLF4, and thus regulating VEGFR2, ZO‐1, occludin and CLDN5 expression to enhance vascular leakiness	Zeng et al 56
	Breast cancer cells	Annexin A6	Lung tissues (unspecified)	Induction of CCL2 expression, and expansion of Ly6C+CCR2+ monocytes	Keklikoglou et al 57
	Lung carcinoma cells	EV‐associated RNAs (unspecified)	Alveolar type II epithelial cells	Activation of TLR3, and increased cytokine secretion and neutrophil recruitment	Liu et al 58
Brain	Breast cancer cells	Unspecified	Brain endothelial cells	Downregulation of rab7 expression to facilitate tumour‐derived EVs passing intact brain‐blood barrier through transcytosis	Morad et al 61
	Breast cancer cells	miRNA‐181c	Brain endothelial cells	Downregulation of PDPK1, induction of cofilin‐modulated actin dynamics interruption and disruption of brain‐blood barrier integrity	Tominaga et al 62
	Lung cancer and breast cancer cells	CEMIP	Brain endothelial and microglial cells	Upregulation of pro‐inflammatory cytokines coded by Ptgs2, Tnf and Ccl/Cxcl, leading to brain vascular niche remodelling	Rodrigues et al 63
	Breast cancer cells	miRNA‐503	Microglial cells	Induction of M1‐M2 polarization and upregulation of immunosuppressive cytokines	Xing et al 64
	Astrocytes	miRNA‐19a	Breast cancer tumour cells	Causing adaptive PTEN loss in cancer cells metastasized to the brain, and leading to tumour outgrowth through CCL2 upregulation and recruitment of IBA1‐expressing myeloid cells	Zhang et al 65
Bone	Prostate cancer cells	EV‐associated RNA (both mRNAs and miRNAs)	Osteoblasts	Increased osteoblast viability and an enhanced growth environment	Probert et al 70
	Lung adenocarcinoma cells	miRNA‐21	Osteoclast progenitors	Targeting of Pdcd4 resulting in increased osteoclastogenesis	Xu et al 72
	Prostate cancer cells	miRNA‐940	Human mesenchymal stem cells (hMSCs)	Targeting of ARHGAP1 and FAM134A in hMSCs, resulting in osteoblastic phenotype differentiation	Hashimoto et al 74
	Breast cancer cells	miRNA‐940	hMSCs	Osteogenic differentiation of hMSCs resulting in osteoblastic lesions in resultant metastatic tumour	Hashimoto et al 74
	Melanoma cells	c‐MET	Bone marrow progenitor cells	Differentiation of bone marrow progenitor cells into pro‐vasculogenic phenotypes	Peinado et al 75
Liver	Breast cancer and melanoma cells	Integrin α V β 5	F4/80‐positive Kupffer cells	Upregulation of pro‐inflammatory gene expression S100P, A8	Hoshino et al 51
	Pancreatic ductal adenocarcinoma	MIF	Kupffer cells	Stimulation of TGFß production by Kupffer cells, and activation of hepatic stellate cells	Costa‐Silva et al 80
	Colorectal cancer cells	miRNA‐21	Liver macrophages	Induction of IL‐6‐secreting phenotype via TLR7 pathways	Shao et al 81
	Gastric cancer cells	EGFR	Liver stromal cells	Downregulation of miRNA‐26a/b leading to activation of hepatocyte growth factor	Zhang et al 82
	Colorectal cancer cells	miRNA‐25‐3p	Endothelial cells	Targets KLF2 and KLF4, thus regulating VEGFR2, ZO‐1, occluding and CLDN5 expression	Zeng et al 56