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001-es BibID:BIBFORM073532
Első szerző:Barok Márk (biofizikus)
Cím:Cancer-derived exosomes from HER2-positive cancer cells carry trastuzumab-emtansine into cancer cells leading to growth inhibition and caspase activation / Mark Barok, Maija Puhka, Gyorgy Vereb, Janos Szollosi, Jorma Isola, Heikki Joensuu
Dátum:2018
ISSN:1471-2407
Megjegyzések:Background: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that carries a cytotoxic drug (DM1) toHER2-positive cancer. The target of T-DM1 (HER2) is present also on cancer-derived exosomes. We hypothesizedthat exosome-bound T-DM1 may contribute to the activity of T-DM1.Methods: Exosomes were isolated from the cell culture medium of HER2-positive SKBR-3 and EFM-192A breast cancercells, HER2-positive SNU-216 gastric cancer cells, and HER2-negative MCF-7 breast cancer cells by serial centrifugationsincluding two ultracentrifugations, and treated with T-DM1. T-DM1 not bound to exosomes was removed using HER2-coated magnetic beads. Exosome samples were analyzed by electron microscopy, flow cytometry and Westernblotting. Binding of T-DM1-containing exosomes to cancer cells and T-DM1 internalization were investigated withconfocal microscopy. Effects of T-DM1-containg exosomes on cancer cells were investigated with the AlamarBluecell proliferation assay and the Caspase-Glo 3/7 caspase activation assay.Results: T-DM1 binds to exosomes derived from HER2-positive cancer cells, but not to exosomes derived fromHER2-negative MCF-7 cells. HER2-positive SKBR-3 cells accumulated T-DM1 after being treated with T-DM1-containgexosomes, and treatment of SKBR-3 and EFM-192A cells with T-DM1-containing exosomes resulted in growth inhibitionand activation of caspases 3 and/or 7.Conclusion: T-DM1 binds to exosomes derived from HER2-positive cancer cells, and T-DM1 may be carried toother cancer cells via exosomes leading to reduced viability of the recipient cells. The results suggest a new mechanismof action for T-DM1, mediated by exosomes derived from HER2-positive cancer.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Breast cancer
Trastuzumab-emtansine
T-DM1
HER2
Exosome
Megjelenés:Bmc Cancer. - 18 : 1 (2018), p. 504-516. -
További szerzők:Puhka, Maija Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus) Isola, Jorma Joensuu, Heikki
Pályázati támogatás:GINOP-2.3.2-15-2016-00020
GINOP
GINOP-2.3.2-15-2016-00050
GINOP
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