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Cancer-derived exosomes from HER2-positive cancer cells carry trastuzumab-emtansine into cancer cells leading to growth inhibition and caspase activation

Overview of attention for article published in BMC Cancer, May 2018
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Title
Cancer-derived exosomes from HER2-positive cancer cells carry trastuzumab-emtansine into cancer cells leading to growth inhibition and caspase activation
Published in
BMC Cancer, May 2018
DOI 10.1186/s12885-018-4418-2
Pubmed ID
Authors

Mark Barok, Maija Puhka, Gyorgy Vereb, Janos Szollosi, Jorma Isola, Heikki Joensuu

Abstract

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that carries a cytotoxic drug (DM1) to HER2-positive cancer. The target of T-DM1 (HER2) is present also on cancer-derived exosomes. We hypothesized that exosome-bound T-DM1 may contribute to the activity of T-DM1. Exosomes were isolated from the cell culture medium of HER2-positive SKBR-3 and EFM-192A breast cancer cells, HER2-positive SNU-216 gastric cancer cells, and HER2-negative MCF-7 breast cancer cells by serial centrifugations including 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 Western blotting. Binding of T-DM1-containing exosomes to cancer cells and T-DM1 internalization were investigated with confocal microscopy. Effects of T-DM1-containg exosomes on cancer cells were investigated with the AlamarBlue cell proliferation assay and the Caspase-Glo 3/7 caspase activation assay. T-DM1 binds to exosomes derived from HER2-positive cancer cells, but not to exosomes derived from HER2-negative MCF-7 cells. HER2-positive SKBR-3 cells accumulated T-DM1 after being treated with T-DM1-containg exosomes, and treatment of SKBR-3 and EFM-192A cells with T-DM1-containing exosomes resulted in growth inhibition and activation of caspases 3 and/or 7. T-DM1 binds to exosomes derived from HER2-positive cancer cells, and T-DM1 may be carried to other cancer cells via exosomes leading to reduced viability of the recipient cells. The results suggest a new mechanism of action for T-DM1, mediated by exosomes derived from HER2-positive cancer.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 80 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 80 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 19%
Researcher 11 14%
Student > Master 10 13%
Student > Bachelor 9 11%
Student > Postgraduate 4 5%
Other 13 16%
Unknown 18 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 20 25%
Agricultural and Biological Sciences 11 14%
Pharmacology, Toxicology and Pharmaceutical Science 8 10%
Medicine and Dentistry 7 9%
Chemistry 5 6%
Other 8 10%
Unknown 21 26%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 May 2018.
All research outputs
#11,468,330
of 12,902,279 outputs
Outputs from BMC Cancer
#3,922
of 4,795 outputs
Outputs of similar age
#233,686
of 269,550 outputs
Outputs of similar age from BMC Cancer
#1
of 1 outputs
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