Physical nanoscale conduit-mediated communication between tumour cells and the endothelium modulates endothelial phenotype
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Connor-2015-Physical nanoscale.pdf
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Author(s)
Connor, Yamicia
Tekleab, Sarah
Nandakumar, Shyama
Walls, Cherelle
Tekleab, Yonatan
Husain, Amjad
Gadish, Or
Sabbisetti, Venkata
Kaushik, Shelly
Sehrawat, Seema
Date Issued
December 2015
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Connor, Yamicia, Sarah Tekleab, Shyama Nandakumar, Cherelle Walls, Yonatan Tekleab, Amjad Husain, Or Gadish, et al. “Physical Nanoscale Conduit-Mediated Communication Between Tumour Cells and the Endothelium Modulates Endothelial Phenotype.” Nat Comms 6 (December 16, 2015): 8671. © 2015 Macmillan Publishers Limited
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Final published version
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Aeronautics and Astronautics
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DOI of Published Version
https://doi.org/10.1038/ncomms9671
