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Regeneration Enhances Metastasis: A Novel Role for Neurovascular Signaling in Promoting Melanoma Brain Metastasis

Authors :
Roshini Prakash
Sivan Izraely
Nikita S. Thareja
Rex H. Lee
Maya Rappaport
Riki Kawaguchi
Orit Sagi-Assif
Shlomit Ben-Menachem
Tsipi Meshel
Michal Machnicki
Shuichi Ohe
Dave S. Hoon
Giovanni Coppola
Isaac P. Witz
S. Thomas Carmichael
Source :
Frontiers in Neuroscience, Vol 13 (2019)
Publication Year :
2019
Publisher :
Frontiers Media S.A., 2019.

Abstract

Neural repair after stroke involves initiation of a cellular proliferative program in the form of angiogenesis, neurogenesis, and molecular growth signals in the surrounding tissue elements. This cellular environment constitutes a niche in which regeneration of new blood vessels and new neurons leads to partial tissue repair after stroke. Cancer metastasis has similar proliferative cellular events in the brain and other organs. Do cancer and CNS tissue repair share similar cellular processes? In this study, we identify a novel role of the regenerative neurovascular niche induced by stroke in promoting brain melanoma metastasis through enhancing cellular interactions with surrounding niche components. Repair-mediated neurovascular signaling induces metastatic cells to express genes crucial to metastasis. Mimicking stroke-like conditions in vitro displays an enhancement of metastatic migration potential and allows for the determination of cell-specific signals produced by the regenerative neurovascular niche. Comparative analysis of both in vitro and in vivo expression profiles reveals a major contribution of endothelial cells in mediating melanoma metastasis. These results point to a previously undiscovered role of the regenerative neurovascular niche in shaping the tumor microenvironment and brain metastatic landscape.

Details

Language :
English
ISSN :
1662453X
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Neuroscience
Publication Type :
Academic Journal
Accession number :
edsdoj.875cfc223ce44d52a9237b6450bb178c
Document Type :
article
Full Text :
https://doi.org/10.3389/fnins.2019.00297