title: Physical nanoscale conduit-mediated communication between tumour cells and the endothelium modulates endothelial phenotype.
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.
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.|Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Medicine, Brigham and Women's Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA.|Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Yamicia
authors.initials: Y
authors.lastname: Connor
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Tekleab
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA.
authors.forename: Shyama
authors.identifier: http://orcid.org/0000-0003-0624-3452
authors.initials: S
authors.lastname: Nandakumar
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA.
authors.forename: Cherelle
authors.initials: C
authors.lastname: Walls
authors.affiliation: Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Tekleab
authors.affiliation: Harvard Medical School, Boston, Massachusetts 02115, USA.|Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
authors.forename: Amjad
authors.initials: A
authors.lastname: Husain
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.|Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Or
authors.initials: O
authors.lastname: Gadish
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA.|Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Venkata
authors.initials: V
authors.lastname: Sabbisetti
authors.affiliation: India Innovation Research Center, New Delhi 110092, India.
authors.forename: Shelly
authors.initials: S
authors.lastname: Kaushik
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Sehrawat
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.|Department of Medicine, Brigham and Women's Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA.|Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Kulkarni
authors.affiliation: Harvard Medical School, Boston, Massachusetts 02115, USA.|Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
authors.forename: Harold
authors.initials: H
authors.lastname: Dvorak
authors.affiliation: Harvard Medical School, Boston, Massachusetts 02115, USA.|Program in Vascular Biology and Department of Surgery, Children's Hospital, Boston, Massachusetts 02115, USA.|Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Zetter
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.|Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Medicine, Brigham and Women's Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA.|Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Elazer
authors.initials: E
authors.lastname: R Edelman
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.|Department of Medicine, Brigham and Women's Hospital, 65 Landsdowne Street, Room 317, Boston, Massachusetts 02115, USA.|Harvard Medical School, Boston, Massachusetts 02115, USA.|Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Shiladitya
authors.initials: S
authors.lastname: Sengupta
mesh_terms: D002448:Cell Adhesion; D002450:Cell Communication; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology*