Physical nanoscale conduit-mediated communication between tumour cells and the endothelium modulates endothelial phenotype
Author(s)
Connor, Yamicia; Tekleab, Sarah; Nandakumar, Shyama; Walls, Cherelle; Tekleab, Yonatan; Husain, Amjad; Gadish, Or; Sabbisetti, Venkata; Kaushik, Shelly; Sehrawat, Seema; Kulkarni, Ashish; Dvorak, Harold; Zetter, Bruce; Sengupta, Shiladitya; Edelman, Elazer R.; ... Show more Show less
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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.
Date issued
2015-12Department
Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Aeronautics and AstronauticsJournal
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
Version: Final published version
ISSN
2041-1723