Stromal Endothelial Cells Directly Influence Cancer Progression
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Edelman_Stromal endothelial.pdf
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Author(s)
Franses, Joseph Wang
Baker, Aaron B.
Chitalia, Vipul C.
Edelman, Elazer R.
Date Issued
January 2011
Journal
Science Translational Medicine
Publisher
American Association for the Advancement of Science
Citation
Franses, J. W., A. B. Baker, V. C. Chitalia, and E. R. Edelman. “Stromal Endothelial Cells Directly Influence Cancer Progression.” Science Translational Medicine 3, no. 66 (January 19, 2011): 66ra5-66ra5.
Version
Author's final manuscript
Abstract
Cancer growth and metastasis are regulated in part by stromal cells such as fibroblasts and immune cells within the tumor microenvironment. Endothelial cells (ECs) are also ubiquitous within tumors because tumors are vascular, and yet, the impact of tumor-resident ECs is less well understood. Through paracrine regulation, ECs modulate a diverse spectrum of pathophysiologic processes in normal and hyperplastic tissues. We hypothesized that ECs offer similar paracrine regulatory control of cancer biology. Indeed, secretions from quiescent ECs muted the proliferative and invasive phenotype of lung and breast cancer cells in vitro and reduced cancer cell protumorigenic and proinflammatory signaling. EC perlecan silencing significantly changed this regulatory relationship, eliminating the ability of ECs to inhibit cancer cell invasiveness via increased interleukin-6 secretion. Moreover, implanting ECs embedded within porous matrices slowed adjacent xenograft tumor growth and prevented architectural degeneration, with a concomitant reduction in proliferative and tumorigenic markers. Finally, lung carcinoma cells pretreated with intact EC-conditioned media, but not media conditioned with perlecan-silenced ECs, exhibited reduced micrometastatic burden after tail vein injection. These findings add to an emerging appreciation of EC-regulatory effects that transcend their structural roles and pave the way for improved characterization and control of EC-cancer cross-talk interactions for diagnosis, prognosis, and treatment of cancer.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1126/scitranslmed.3001542
