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Nat Commun. 2015 Dec 16;6:8671. doi: 10.1038/ncomms9671.

Physical nanoscale conduit-mediated communication between tumour cells and the endothelium modulates endothelial phenotype.

Author information

1
Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.
2
Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
3
Department of Medicine, Brigham and Women's Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA.
4
Harvard Medical School, Boston, Massachusetts 02115, USA.
5
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
6
India Innovation Research Center, New Delhi 110092, India.
7
Program in Vascular Biology and Department of Surgery, Children's Hospital, Boston, Massachusetts 02115, USA.
8
Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.

Abstract

Metastasis is a major cause of mortality and remains a hurdle in the search for a cure for cancer. Not much is known about metastatic cancer cells and endothelial cross-talk, which occurs at multiple stages during metastasis. Here we report a dynamic regulation of the endothelium by cancer cells through the formation of nanoscale intercellular membrane bridges, which act as physical conduits for transfer of microRNAs. The communication between the tumour cell and the endothelium upregulates markers associated with pathological endothelium, which is reversed by pharmacological inhibition of these nanoscale conduits. These results lead us to define the notion of 'metastatic hijack': cancer cell-induced transformation of healthy endothelium into pathological endothelium via horizontal communication through the nanoscale conduits. Pharmacological perturbation of these nanoscale membrane bridges decreases metastatic foci in vivo. Targeting these nanoscale membrane bridges may potentially emerge as a new therapeutic opportunity in the management of metastatic cancer.

PMID:
26669454
PMCID:
PMC4697439
DOI:
10.1038/ncomms9671
[Indexed for MEDLINE]
Free PMC Article

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