TABLE 2.

The role of exosomes in angiogenesis and vascular permeability.

Phenotype	Type of primary cancer	Contents in exosomes	Target organ/cells	Specific mechanism	References
Angiogenesis	Breast cancer	miR-105	Lung/Brain microvascular ECs	Downregulating microvascular ECs expression of ZO-1; destroying the endothelial barriers and vascular integrity; increasing vascular permeability	Zhou et al. (2014)
	Breast cancer/lung cancer	CEMIP	Brain ECs/microglial cells	Upregulating cytokines Ptgs2, Tnf, and Ccl/Cxcl; promoting vascular remodeling and angiogenesis	Rodrigues et al. (2019)
	Glioblastoma	Pro-angiogenic VEGF-A factor	Brain ECs	Fostering brain ECs both angiogenesis and permeability	Treps et al. (2017)
	HCC	miR-638, miR-663a, miR-3648, miR-4258	Intrahepatic ECs	Downregulating ECs expression of ZO-1 and VE-cadherin; increasing vascular permeability	Chen et al. (2018)
	HCC	NID1	Lung fibroblasts	Enhancing angiogenesis and pulmonary endothelial permeability	Mao et al. (2020)
	Melanoma	uPAR	ECs	Enhancing VE-Cadherin, EGFR, and uPAR expression and pro-angiogenic effects	Biagioni et al. (2021)
	CRC	miR-25-3p	Liver/lung ECs	Upregulating ECs expression of VEGFR2 and downregulating the level of ZO-1, occludin, and Claudin5 by silencing KLF2/KLF4	Zeng et al. (2018)
	CRC	ANGPTL1	Liver Kupffer cells	Regulating the Kupffer cells’ secretion pattern by inhibiting the JAK2-STAT3 signaling pathway and decreasing the MMP9 expression to prevent vascular leakiness	Jiang et al. (2021)
	Cholangiocarcinoma	circ-CCAC1	HUVECs	Entering HUVECs and sequestering EZH2 to modulate SH3GL2/ZO-1/Occludin signaling and reducing the levels of TJs protein; destroying vascular endothelial barriers and inducing angiogenesis	Xu et al. (2020)
	Cervical squamous cancer	Exosomal microRNA-independent	HUVECs	Inducing endoplasmic reticulum stress in HUVECs; increasing PERK and eIF2α and downregulating TJ proteins	Lin et al. (2020)
Angiogenesis under hypoxia condition	Myeloma	miR-135b	ECs	Targeting HIF-1 and enhancing angiogenesis	Umezu et al. (2014)
	Leukemia	miR-210	HUVECs	Enhancing the tube formation in HUVECs	Tadokoro et al. (2013)
	Lung cancer	miR-23a	ECs	The accumulation of HIF-1α in ECs via directly suppressed PHD1 and 2; ZO-1 was inhibited; Vascular permeability and angiogenesis was enhanced	Hsu et al. (2017)
	Lung cancer	miR-494	ECs	Suppressing PTEN by activating Akt/eNOS pathway in ECs and reshape the angiogenesis.	Mao et al. (2015)
	ESCC	—	HUVECs	Promoting HUVECs tube formation	Mao et al. (2019)

Abbreviation: ECs, endothelial cells; ZO-1, zonula occludens-1; CEMIP, cell migration-inducing and hyaluronan-binding protein; miRNA, microRNA; VEGF, vascular endothelial growth factor; HCC, hepatocellular carcinoma; VE-cadherin, vascular endothelial-cadherin; NID1, Nidogen 1; uPAR, urokinase plasminogen activator receptor; CRC, colorectal cancer; ANGPTL1, angiopoietin-like protein 1; MMPs, Matrix metalloproteinases; circ-CCAC1,cholangiocarcinoma-associated circular RNA 1; HUVECs, human umbilical vein endothelial cells; PERK, phosphorylation of protein kinase RNA-like ER kinase; eIF2, eukaryotic translation initiation factor 2 alpha; PHD1 and 2, prolyl hydroxylase 1 and 2; ESCC, esophageal squamous cell carcinoma.