Table 1.
Biomolecules contained in exosomes and their effect on angiogenesis and metastasis.
| Affected Process | Source of Exosomes | Molecular Cargo | Role in Cancer Development | Ref. |
|---|---|---|---|---|
| Angiogenesis | Gastric cancer patients (GC) | miR-155 | Exosome miR-155 inhibit FOXO3a expression promoting angiogenesis and progression in GC. Potential biomarker for migration, angiogenesis, and poor prognosis.Novel target for anti-angiogenesis therapy | [79] |
| Exosome miR-155 downregulate c-MYB and upregulate VEGF expression promoting growth, angiogenesis and metastasis in GC. | [80] | |||
| Nasopharyngeal cancer (NPC) | miR-17-5p | Exosome miR-17-5p promotes angiogenesis in NPC though inhibition of BAMBI expression and regulation of AKT/VEGF-A signaling. | [81] | |
| Mir-23a | Overexpression of Exosome miR-23a in NPC promote angiogenesis in vitro and in vivo by targeting the testis-specific gene antigen (TSGA10), an angiogenesis inhibitor. | [82] | ||
| Melanoma | miR-155 | Overexpression of Exosome miR-155 in melanoma reprogram fibroblasts into CAFs by targeting SOCS1, which activates JAK2/STAT3 signaling pathway and increase the expression levels of VEGFa, FGF2, and MMP9 in fibroblasts promoting angiogenesis.Potential therapeutic target to inhibit melanoma angiogenesis. | [83] | |
| Ovarian carcinoma (OC) | miR-205 | Exosome miR-205 from OC cells promote metastasis by inducing angiogenesis in vitro and in vivo via the PTEN-AKT pathway. Potential therapeutic target for OC. | [84] | |
| Non-small cell lung carcinoma (NSCLC) | miR-619-5p | Exosome miR-619-5p promotes NSCLCs growth and metastasis by regulating RCAN1.4, a tumor suppressor protein. | [85] | |
| Chondrosarcoma | lncRNA RAMP2-AS1 | Exosome lncRNA RAMP2-AS1 from chondrosarcoma cells promotes angiogenesis proliferation, migration and tube formation favoring by the RAMP2-AS1/miR-2355-5p/VEGFR2 axis in human umbilical vein endothelial cells (HUVEC). | [86] | |
| Metastasis | Gastric cancer (GC) | miR-27a | Exosome miR-27a from GC cells induce fibroblasts reprogramming into CAFs, promoting proliferation, motility, and metastasis in vitro and in vivo, and over-expression of miR-27a on CAFs derived exosomes could increase the malignant behavior of GC cells. miR-27a also downregulate CSRP2, increasing GC cells proliferation and motility. | [87] |
| Oral squamous cell carcinoma (OSCC) | miR-34a-5p | Exosome miR-34a-5p from OSCC binds to AXL to inhibit the tumorigenesis suppressing tumor cell proliferation and metastasis. However, miR-34a-5p in CAF-derived exosomes was significantly reduced and by this mean, miR-34a-5p/AXL axis may increase aggressiveness in oral cancer cells by inducing EMT to promote metastasis by the AKT/GSK-3β/β-catenin/snail signaling which activate MMP-2 and MMP-9 expression. | [88] | |
| Breast cancer (BC) | miR-181d-5p | CAF-derived exosomes can transfer miR-181d-5p to enhance the aggressiveness of breast cancer by promoting tumor growth via downregulation of CDX2 and HOXA5 to favor cell proliferation, invasion, migration and EMT. | [89] | |
| Hepatocellular carcinoma (HCC). | TGF-β | Exosomes derived from hepatocellular carcinoma cells promote migration and invasion of recipient cells by decreasing E-cadherin expression, increasing vimentin expression and promoting EMT via TGF-β/Smad signaling. | [90] | |
| MALAT1 | Anti-angiogenesis therapies appear to be useful for the treatment of HCC, although metastasis may develop over time. Increased expression of YAP1 around tumor-associated blood vessels indicates a role in angiogenesis for this protein. Its inhibition in endothelial cells reduces proliferation and tube formation. However, inhibition of YAP1 leads to an increase in the release of exosomes containing MALAT1 into the tumor microenvironment. Exosome transfer of MALAT1 to hepatic cells increase invasion and migration via the activation of ERK1/2 signaling. | [91] | ||
| Colorectal cancer(CRC) | lncRNA RPPH1 | lncRNA RPPH1 is upregulated in CRC tissues associated with advanced TNM stages and poor prognosis. RPPH1 promote CRC metastasis in vitro and in vivo by inducing EMT of CRC cells via interacting with β-III tubulin (TUBB3) CRC cell-derived exosomes transport RPPH1 into macrophages mediating M2 polarization, which promotes metastasis and proliferation in CRC cells. | [92] | |
| Lung cancer | miR-499a-5p | MiR-499a-5p was upregulated in highly metastatic lung cancer cell line and in their exosomes promoting cell proliferation, migration and EMT via mTOR pathway.MiR-499a-5p knockdown suppress these processes in vitro supporting the potential diagnostic and therapeutic value of cancer-derived exosome miR-499a-5p. | [93] | |
| Glioma | miR-1246 | Hypoxic glioma-derived exosomes (H-GDE) induce M2 macrophage polarization, which promotes glioma proliferation, migration and invasion in vitro and in vivo.MiR-1246 is the most abundant in H-GDE, and in the CSF of GBM patients, but its expression decreases after tumor resection. M2 macrophage polarization in H-GDE is mediated by miR-1246 targeting of TERF2IP to activate STAT3 and inhibit the NF-κB signaling pathways. | [94] | |
| Clear cell renal cell carcinoma (ccRCC) | ApoC1 | ApoC1 overexpression in ccRCC cells is related to invasion, poor survival and EMT induction, thus promoting metastasis. In contrast, ApoC1 downregulation inhibits these effects. Transfer of exosome ApoC1 from ccRCC to endothelial cells promotes metastasis by activation of STAT3. This metastatic potential is suppressed by inhibition of DPP-4. | [95] |
Legend: FOXO3a, The Forkhead box O-3a; GC, Gastric cancer; c-MYB, MYB proto-oncogene transcription factor; VEGF, Vascular Endothelial Growth Factor; BAMBI, BMP and Activin Membrane Bound Inhibitor; PTEN, Phosphatase and tensin homolog; AKT, serine-threonine protein kinase; TSGA10, Testis-Specific 10; CAFs, Cancer-associated fibroblasts; FGF2, Fibroblast Growth Factor 2; MMP9, Matrix Metallopeptidase 9; OC, Ovarian cancer; RCAN1.4, Regulator of Calcineurin 1 Isoform 4; RAMP2-AS1, RAMP2 Antisense RNA 1; HUVECs, Human umbilical vein endothelial cells; CSRP2,Cysteine And Glycine Rich Protein 2; OSCC, Oral squamous cell carcinoma; AXL, AXL Receptor Tyrosine Kinase; GSK-3β, Glycogen Synthase Kinase 3 Beta; CDX2, Caudal Type Homeobox 2; HOXA5, Homeobox A5; EMT, Epithelial-Mesenchymal Transition; TGF-β, Transforming Growth Factor Beta; MALAT1, Metastasis Associated Lung Adenocarcinoma Transcript 1; ERK1/2, The extracellular signal-regulated kinase 1/2; YAP1, Yes 1 Associated Transcriptional Regulator; RPPH1, Ribonuclease P RNA Component H1; TNM, Tumor, Node, Metastases; GBM, Glioblastoma; TERF2IP, TERF2 Interacting Protein; ApoC1, Apolipoprotein C1; STAT3, Signal Transducer And Activator of Transcription 3.