Table 1.
A list of targets for blocking/stimulation of exosomal release and uptake for cancer therapeutics.
| Targets | Source of exosomes | Targeting agent | Functionality | Ref. |
|---|---|---|---|---|
| Calcium (Ca2+) | Breast cancer cells | Munc13-4 | Calcium stimulates exosome secretion through upregulation of Munc13-4 protein in metastatic cells | [129] |
| Previous presence of exosomes in the environment | Normal mammary epithelial cells (HMEC B42) | - | Exosomes from HMEC B42 cells inhibit exosome secretion of breast cancer cells | [130] |
| Differentiation of cancer cells | Colorectal cancer cells (HT29) | Sodium butyrate (NaBu) | Colorectal Cancer cell differentiation induced by NaBu promote increased secretion of exosomes and their expression of CD133 | [131] |
| Tetraspanin-6 (TSPN6) | Breast cancer cells (MCF-7) | SCD4-FL and SDC4-CTF proteins | High levels of TSPN6 inhibit exosome secretion due their binding with SDC4-FL and SDC4-CTF proteins | [132] |
| Integrin beta 3 (ITGB3) | Breast cancer cells (MDA.MB.231) | Dynamin and focal adhesion kinase (FAK) | ITGB3 on the surface of target cell interacts with HSPGs in exosome membrane promoting dynamin and FAK expression to induce exosome uptake | [133] |
| Time of incubation and exosome concentration | Bladder cancer cells (SW780) | Heparin | Long incubation times and high exosome concentrations increase the uptake process. Heparin treatment can block the exosome uptake | [134] |
| Dynamin2 | Erythroleukemia cells (K562) and HTLV-transformed T-cells leukemia cells (MT4) | Knockdown of dynamin2 (Dyn2) | Cellular internalization of exosomes via phagocytosis is inhibited with the knockdown of dynamin2 | [135] |
| Preferential uptake, time of incubation and exosome concentration | Pancreatic cancer cells (PANC-1) | – | PANC-1 cells prefer uptake their own exosomes rather than exosomes derived from other cells. The exosome uptake is time- and dose- dependent | [136] |
| Preferential uptake | Mesenchymal stem cells | – | Placental mesenchymal stem cells make selective uptake of exosomes secreted by the same type of cells | [137] |
| Preferential uptake, clathrin-dependent endocytosis, phagocytosis and macropinocytosis | Ovarian cancer cells (SKOV3) | Inhibitors such as chlorpromazine, cytochalasin D and EIPA | SKOV3 cells internalize preferentially exosomes derived by them. Treatment with chlorpromazine, cytochalasin D and EIPA significantly decrease exosome uptake | [138] |
| Preferential uptake | Fibrosarcoma cells (HT1080) and cervical cancer cells (HeLa) | – | HT1080 and HeLa cells uptake preferentially exosomes from the same origin | [139] |