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

Nature Communications - Tập 6 Số 1
Yamicia Connor1, Sarah Tekleab2, Shyama Nandakumar2, Cherelle Walls2, Yonatan Tekleab3, Amjad Husain4, Or Gadish3, Venkata Sabbisetti2, Shelly Kaushik5, Seema Sehrawat2, Ashish Kulkarni2, Harold F. Dvorak4, Bruce R. Zetter4, Elazer R. Edelman2, Shiladitya Sengupta2
1Harvard-MIT Division of Health Sciences and Technology, Cambridge, 02139, Massachusetts, USA
2Department of Medicine, Brigham and Women's Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA,
3Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA
4Harvard Medical School, Boston, 02115, Massachusetts, USA
5India Innovation Research Center, New Delhi, 110092, India

Tóm tắt

AbstractMetastasis 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.

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