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

Yamicia Connor, Sarah Tekleab, Shyama Nandakumar, Cherelle Walls, Yonatan Tekleab, Amjad Husain, Or Gadish, Venkata Sabbisetti, Shelly Kaushik, Seema Sehrawat, Ashish Kulkarni, Harold Dvorak, Bruce Zetter, Elazer R. Edelman and Shiladitya Sengupta ()
Additional contact information
Yamicia Connor: Harvard-MIT Division of Health Sciences and Technology
Sarah Tekleab: Brigham and Women’s Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA
Shyama Nandakumar: Brigham and Women’s Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA
Cherelle Walls: Brigham and Women’s Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA
Yonatan Tekleab: Massachusetts Institute of Technology
Amjad Husain: Harvard Medical School
Or Gadish: Harvard-MIT Division of Health Sciences and Technology
Venkata Sabbisetti: Brigham and Women’s Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA
Shelly Kaushik: India Innovation Research Center
Seema Sehrawat: Brigham and Women’s Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA
Ashish Kulkarni: Harvard-MIT Division of Health Sciences and Technology
Harold Dvorak: Harvard Medical School
Bruce Zetter: Harvard Medical School
Elazer R. Edelman: Harvard-MIT Division of Health Sciences and Technology
Shiladitya Sengupta: Harvard-MIT Division of Health Sciences and Technology

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9671

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