Table 3.
Effects of hypoxia on EVs in cancer.
| Cancer Disease | Source of EVs | Functions of Released EVs | Biomolecules Carried by Hypoxic EVs | References |
|---|---|---|---|---|
| Prostate cancer (PCA) | LNCaP and PC3 human PCA cells | Invasiveness, motility and stemness of naïve PCA cells; metalloproteinase activity; remodeling of epithelial adherens junction pathways; induction of CAF-type phenotype in prostate fibroblasts; PCA growth and invasiveness | Proteins: MMP-9, MMP-2, TGF-β2, TNF1α, IL6, TSG101, Akt, ILK1, β-catenin; triglycerides | [69,94] |
| Epidermoid carcinoma | A431 human squamous carcinoma cells | Angiogenesis; metastasis | not described | [26] |
| Glioblastoma multiforme (GBM) | U87-MG human GBM cells; plasma of tumor-bearing mice; plasma of GBM patients | Pro-angiogenic effects | mRNAs: ADM, LOX, IGFPB, BCL, BNIP3, NDRG1, PLOD2, PAI1; proteins: IL8, IGFBP1, IGFBP3; MMP9, PTX3, PDGF-AB/AA, CD26, PAI1, CAV1 | [93] |
| Breast cancer | U87-MG human GBM cells | Tumor development; angiogenesis | TF | [92] |
| MCF-7, MDA-MB-231, MDA-MB-435 human breast cancer cells | Endothelial cell tubulogenesis; mechanisms of repressing DNA repair | miR-210 | [63] | |
| Focal adhesion formation, invasion and metastasis | not described | [22] | ||
| 4T1 mouse breast cancer cells | Angiogenesis | miR-210 | [90] | |
| Leukemia | K562 human leukemia cells | HUVECs tube formation | miR-210 | [84] |
| Multiple myeloma | RPMI8226, KMS-11, U266 human multiple myeloma cells | Tube formation; angiogenesis; regulation of FIH molecular pathway | miR-210, miR135b | [85] |
| Lung cancer | CL1-5 human lung cancer cells | Local and distant angiogenesis; increased vascular permeability; cancer transendothelial migration | miR-23a | [86] |
| NCI-H1688 human small cell lung cancer and NCI-H2228 human non-small cell lung cancer | Migration of endothelial and cancer cells; metastasis | TGF-β and IL-10 | [95] | |
| A549 human lung adenocarcinoma cells | Angiogenesis, metastasis, cancer cell survival, migration and tube formation | miR-135b, miR-210 | [91] | |
| Ovarian cancer | OVCAR-8, A2780, TR127, TR182 human ovarian cancer cells; patient-derived ascites | Tumor progression, metastasis and chemoresistance | STAT3, FAS proteins | [87] |
| Oral squamous cell carcinoma (OSCC) | SCC-9, CAL-27 human OSCC cells; serum of OSCC patients | EMT, migration and invasion of target normoxic cells | miR-21; miR-205, miR-148b (to be investigated) | [11] |
| Nasopharyngeal carcinoma (NPC) | NP69 and AdAH human NPC cells, transfected with latent membrane protein 1 (LMP1) | EMT; cancer progression and invasive potential | HIF1α | [57] |
| Colorectal cancer (CRC) | HT29 and HCT116 human CRC cells | Endothelial cells proliferation and migration; tumor growth and angiogenesis | Wnt4 protein | [97] |
| Melanoma | B16-F0 mouse melanoma cells, A375 human melanoma cells, A431 squamous skin carcinoma cells, A549 lung adenocarcinoma cells | Monocyte/macrophage recruitment in vitro and in vivo and host immunosuppression; tumor cell proliferation | chemokines and growth factors (CSF-1, CCL2, EMAP2, TGFβ, FTH, FTL); miR-let-7a, miR-21a | [66] |
| Hepatocellular carcinoma (HCC) | Huh7 and MHCC-97H human HCC cells | Proliferation, migration, invasiveness, EMT in normoxic HCC cells | miR-1273f, miR-93-5p, miR-221-3p | [88] |
| Pancreatic cancer (PC) | MiaPaCa and AsPC1 PC cell lines | Adaptive survival of PC hypoxic cancer cells | not described | |
| PANC-1, BxPC-3 cell lines; serum of PC patients | M2 polarization of macrophages, metastatic behavior of PC cells in vitro and in vivo | miR-301a-3p | [96] |