Type

Journal Article

Authors

Lorraine O'Driscoll
Marek W Radomski
John Crown
Susan McDonnell
Anne M Friel
Linda Hughes
Robert Wallace
Claire Corcoran
Sweta Rani
Keith O'Brien

Subjects

Biochemistry

Topics
receptors progesterone antigens cd31 cell proliferation reverse transcriptase polymerase chain reaction breast neoplasms receptor erbb 2 microscopy electron transmission ultrastructure humans receptors estrogen blood vessels cell movement female genetics metabolism exosomes matrix metalloproteinase 2 blotting western cell line tumor physiology anoikis matrix metalloproteinase 9 microscopy confocal aged physiopathology middle aged

Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells. (2012)

Abstract Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancers but is responsible for a disproportionate number of deaths. We investigated the relevance, in TNBC, of nano-sized exosomes expelled from cells. Specifically, we compared effects of exosomes derived from the claudin-low TNBC cell line Hs578T and its more invasive Hs578Ts(i)8 variant, as well as exosomes from TNBC patient sera compared to normal sera. Exosomes were isolated from conditioned media (CM) of Hs578T and Hs578Ts(i)8 cells and from sera by filtration and ultracentrifugation. Successful isolation was confirmed by transmission electron microscopy and immunoblotting. Subsequent analysis, of secondary/recipient cells in response to exosomes, included proliferation; motility/migration; invasion; anoikis assays and endothelial tubule formation assays. Hs578Ts(i)8-exosomes versus Hs578T-exosomes significantly increased the proliferation, migration and invasion capacity of all three recipient cell lines evaluated i.e. SKBR3, MDA-MB-231 and HCC1954. Exosomes from Hs578Ts(i)8 cells also conferred increased invasiveness to parent Hs578T cells. Hs578Ts(i)8-exosomes increased sensitivity of SKBR3, MDA-MB-231 and HCC1954 to anoikis when compared to the effects of Hs578T-exosomes reflecting the fact that Hs578Ts(i)8 cells are themselves innately more sensitive to anoikis. In relation to vasculogenesis and subsequent angiogenesis, Hs578Ts(i)8-exosomes versus Hs578T-exosomes stimulated significantly more endothelial tubules formation. Finally, our pilot translational study showed that exosomes from TNBC patients' sera significantly increased recipient cells' invasion when compared to those derived from age- and gender-matched healthy control sera. This study supports the hypothesis that TNBC exosomes may be involved in cancer cell-to-cell communication, conferring phenotypic traits to secondary cells that reflect those of their cells of origin.
Collections Ireland -> Trinity College Dublin -> PubMed

Full list of authors on original publication

Lorraine O'Driscoll, Marek W Radomski, John Crown, Susan McDonnell, Anne M Friel, Linda Hughes, Robert Wallace, Claire Corcoran, Sweta Rani, Keith O'Brien

Experts in our system

1
Lorraine O'Driscoll
Trinity College Dublin
Total Publications: 164
 
2
Marek W Radomski
Trinity College Dublin
Total Publications: 44
 
3
John Crown
Dublin City University
Total Publications: 104
 
4
Susan McDonnell
University College Dublin
Total Publications: 26
 
5
Claire Corcoran
Trinity College Dublin
 
6
Sweta Rani
Trinity College Dublin