Table 1.

Outline of BC-derived exosomal cargos and biological functions, clinical values in BC metastasis.

Exosomal contents	Expression	Recipient cells	Mechanisms	Biological function	Clinic values	Ref.
miR-130a-3p	Downregulation	High-metastatic BC cells	Directly regulate RAB5B/EGFR signaling pathways	Inhibit BCSCs proliferation and migration	A noninvasive molecular marker for the diagnosis and prognosis of BC	40
miR-770	Downregulation	TAMs	Increase the STMN1 expression	Inhibit TNBC migration and invasion	A prognostic biomarker in TNBC	41
Let-7a	Downregulation	High-metastatic BC cells	Silence the c-Myc expression	Inhibit the proliferation and migration of TNBC cells	A possible therapy target of BC	42
miR-188-5p	Downregulation	High-metastatic BC cells	Selective sorting into exosomes and regulate its target IL6ST	Inhibit BC-cell migration	A possible diagnostic biomarker of BC	43
miR-155	Upregulation	Adipocytes and muscle cells	Induce lipolysis and muscle loss	Leading to cancer-associated cachexia	A possible therapy target of BC	44
miR-222	Upregulation	Low-metastatic BC cells	Downregulate tumor suppressor gene PDLIM2 and activate NF-kB	Correlate to BC patients with lymphatic metastasis	A potential approach of therapeutic strategies for advanced BC	45
miR-146a	Upregulation	NFs	Enhance the transformation of NFs into CAFs via TXNIP/Wnt pathways	Accelerate invasion of BC cells	A possible therapy target of BC	46
miR-1910-3p	Upregulation	Mammary epithelial cells	Regulate MTMR3 and activate the NF-κB signaling pathway	Promote growth and metastasis of BC cells	A new molecular marker for BC diagnosis	47
miR-200c miR-141	Upregulation	N/A	N/A	N/A	Potential biomarkers for early detection of BC metastasis	48
miR-205	Downregulation	N/A	Potentiate the inflammatory responses	Attenuate BC metastasis	A possible therapy target of BC	50
miR-9	Upregulation	Low-metastatic BC cells	Target tumor suppressors PTEN	Enhance metastatic phenotype of BC	A possible therapy target of BC	51,52
miR-155	Upregulation	Low-metastatic BC cells	Potentiate the inflammatory responses; Target tumor suppressors DUSP14	Enhance metastatic phenotype of BC	A possible therapy target of BC	50–52
miR-7641	Upregulation	Low-metastatic BC cells	Induce epigenetic modulation	Promote BC-cell proliferation and invasion	A diagnostic biomarker and therapy target of BC	53
miR-22-3p	Upregulation	HUVECs	Mediate tumor vessel abnormalization by suppressing transgelin	Promote tumor budding and BC progression	A potential therapeutic target for BC	54
miR-145	Downregulation	HUVECs	Target IRS1 and inhibit the angiogenesis of HUVECs	Weaken angiogenesis	A possible therapy target of BC	21
miR-939	Upregulation	Endothelial cells	Target VE-cadherin	Increase tumor cell trans-endothelial migration	A possible therapy target of BC	55
miR-105	Upregulation	Endothelial cells	Damage the integrity of natural barriers by targeting ZO-1	Benefit for BC metastasis	Biomarkers in the circulation	56
miR-21 miR-105	Upregulation	N/A	N/A	N/A	Potential biomarkers for BC metastasis	57
miR-20a-5p	Upregulation	BMMs	Facilitate the osteoclastogenesis by targeting SRCIN1	Promote the migration and invasion of MDA-MB-231 cells	A potential target for BC therapy	58
miR-21	Upregulation	Osteoclast	Boost osteoclastogenesis via regulating PDCD4 protein levels	Promote BC bone metastasis	A potential target for BC therapy and diagnosis	59
miR-183-5p	Upregulation	Macrophages	Promote the secretion of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α via repressing PPP2CA	Promote BC growth and metastasis	A potential target in tumor therapies	60
miR-33	Downregulation	Macrophages	Induce M1 polarization	Inhibit BC growth and metastasis	A potential target for BC therapy	61
miR-4443	Upregulation	Stromal cells	Break the natural barriers via impairing TIMP2 and consequently upregulating MMP-2	Induce BC liver metastasis	A new therapy to inhibit liver metastasis of BC	38
miR-122	Upregulation	Non-tumor cells	Suppress the glucose uptake of non-tumor cells	Reprogram glucose consumption and promote metastasis	A predictive marker and a therapeutic target for metastatic BC	62
miR-503	Upregulation	Microglia	Promote M1–M2 polarization by modulating the STAT 3 and NF-kB pathways	Promote BC brain metastasis	A promising biomarker of BC	63
miR-1246	Upregulation	Non-tumor cells	Inhibit the expression level of cyclin-G2	Boost cell proliferation and invasion of BC	A serum biomarker for BC	64,65
lncRNA BCRT1	Upregulation	Macrophages	Promote M2 polarization	Promote BC metastasis	A potential therapeutic target and prognostic predictor	70
lncRNAGS1-600G8.5	Upregulation	Brain microvascular endothelial cells	Disrupt the permeability of BBB by inhibiting tight junction proteins	Induce BC brain metastasis	A promising therapeutic target for BC brain metastasis	71
hsa-circRNA-00005795	Downregulation	N/A	N/A	Involve in BC metastasis	A new biomarker for predicting metastasis of BC	73
hsa-circRNA-0088088	Upregulation	N/A	N/A	Involve in BC metastasis	A new biomarker for predicting metastasis of BC	73
circ_0004771	Upregulation	N/A	harbor miR-1253 in BC to upregulate DDAH1	Alter BC malignant phenotypes	A potential target for BC therapy	74
Cd38 Slco2a1 Acsl4 Mtdh Fgfr Tgfbr	Upregulation	N/A	N/A	Involve in high BC metastasis	Potential biomarkers for BC and as targets to block metastasis	75
FN	Upregulation	N/A	Interact with tumor-associated leukocytes	Promote 4T1 breast tumor metastasis	Novel therapeutic strategies	77
ENO-1	Upregulation	N/A	gather proteolytic activity on the BC-cell surface	Promote BC progression	N/A	78
MAP17	Upregulation	Low-metastatic BC cells	Increase the EMT	Promote BC metastasis	A novel target for therapy of mBC	32
HBEGF	Upregulation	Low-metastatic BC cells	Hypoxia induce activation of BHLHE40, and promote exosomal secretion of HBEGF	promote BC lung metastasis	Therapeutic target for BC	82
MTA1	Upregulation	Low-metastatic BC cells	Changes to hypoxia and affect estrogen signaling	Enhance BC metastasis	Potential therapeutic strategies for BC	83
AnxA2	Upregulation	Stromal cells; Endothelial cells	Create favorable TME via activation of p38, NF-ĸB, and STAT 3 pathways; promote angiogenesis	Promote BC brain and lung metastasis	Predict prognosis of BC patients	86,87
UCHL1	Upregulation	Low-metastatic BC cells	Upregulate TGF-β/SMAD signaling pathways and promote EMT	Promote BC migration and extravasation	A novel blood marker for early diagnosis of BC	88
HS	Upregulation	N/A	Upregulation of HPSE and HPSE2 expression in lymphocytes	Promote BC metastasis via crosstalk with circulating lymphocytes	A target for tumor prognosis and treatment for BC	90
Myoferlin	Upregulation	Endothelial cells	Alter protein content	Induce HUVEC migration and proliferation	N/A	91
TSP1	Upregulation	Endothelial cells	Disrupt the intercellular integrity; reduce the expression of VE-cadherin and ZO-1	Facilitate the trans-endothelial migration of BC cells	N/A	92
NPNT	Upregulation	Non-tumor cells	Increase adhesion and anchorage-independent growth in an integrin-dependent manner	Promote metastatic BC cells to adhere and colonize in the lung	A potential prognostic marker and a target for BC therapy	94
FGF PDGF	Upregulation	Endothelial cells	Promote angiogenesis	Promote BC metastasis	N/A	95
CEMIP/ KIAA1199	Upregulation	Low-metastatic BC cells, brain stromal cells	Remodel brain vasculature and induce inflammatory brain vascular niche	Support BC brain metastasis	A promising prognostic biomarker and therapeutic target for mBC	96
L-plastin	Upregulation	Non-tumor cells	Stimulate osteoclastogenesis and promote osteolysis	Activate osteoclast and facilitate metastatic bone osteolysis	A diagnostic and prognostic marker	98
ITGB3	Upregulation	Low-metastatic BC cells	Modulate expression of multiple gene about cancer metastasis	Promote BC metastasis	A target for treating BC skeletal metastasis	99
27-OHC	Upregulation	ER-BC cells	N/A	Promote BC metastasis	A useful strategy to treat BC	110
miR-9 miR-181a	Upregulation	Early-stage MDSCs	Mediate JAK/STAT signaling pathway activation by targeting SOCS3 and PIAS3	Promote BC growth and metastasis	A possible therapy target of BC	116
Let-7i miR-142 miR-155	Upregulation	DC	induce the DC maturation	promote BC immune-escape	A possible therapy target of BC	117
PD-L1	Upregulation	CD8+ T-cell	Promote CD8+ T-cell dysfunction	promote BC metastasis	A possible diagnostic biomarker of BC	118

N/A Not applicable, BC breast cancer, BCSCs human breast cancer stem cells, TAMs tumor-associated macrophages, TNBC triple-negative breast cancer, IL6ST interleukin 6 signal transducer, NFs normal fibroblasts, CAFs cancer-associated fibroblasts, TXNIP thioredoxin-interacting protein, MTMR3 myotubularin-related protein 3, PTEN phosphatase and tension homolog, DUSP14 dual-specificity phosphatases 14, VE-cadherin vascular endothelial cadherin, ZO-1 zona occluden-1, PDLIM2 PDZ and LIM domain-containing protein 2, SRCIN1 SRC kinase signaling inhibitor 1, PDCD4 programmed cell death 4, IL-1β interleukin-1β, TNF-α tumor necrosis factor-α, PPP2CA phosphatase 2 catalytic subunit alpha, TIMP2 tissue inhibitor of metalloproteinase 2, MMPs matrix metalloproteinases, BBB blood–brain barrier, DDAH1 dimethylarginine dimethylaminohydrolase 1, FN fibronectin, ENO-1 enolase-1, EMT epithelial–mesenchymal transition, mBC metastatic breast cancer, HBEGF heparin-binding epidermal growth factor, MTA1 metastasis-associated protein 1, AnxA2 annexin A2, TME tumor microenvironment, UCHL1 ubiquitin carboxyl-terminal hydrolase isozyme L1, HS heparan sulfate, HPSE heparinase, HUVEC human umbilical vein endothelial cells, TSP1 thrombospondin-1, NPNT nephronectin, PDGF platelet-derived growth factor, CEMIP cell migration-inducing protein, ITGB3 integrin β3, 27-OHC 27-hydroxycholesterol, ER− estrogen receptor-negative, MDSC myeloid-derived suppressor cells, DC dendritic cells, PD-L1 programmed death-ligand 1.