Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/31883
Title: VEGFR2-Mediated Vascular Dilation as a Mechanism of VEGF-Induced Anemia and Bone Marrow Cell Mobilization
Authors: Lim, S.
Zhang, Y.
Zhang, D.
Chen, F.
Hosaka, K.
Feng, N.
Seki, T.
Andersson, P.
Li, J.
Zang, J.
Sun, B.
Cao, Yihai
First Published: 9-Oct-2014
Publisher: Elsevier (Cell Press)
Citation: Cell Reports Volume 9, Issue 2, 23 October 2014, Pages 569–580
Abstract: Molecular mechanisms underlying tumor VEGF-induced host anemia and bone marrow cell (BMC) mobilization remain unknown. Here, we report that tumor VEGF markedly induced sinusoidal vasculature dilation in bone marrow (BM) and BMC mobilization to tumors and peripheral tissues in mouse and human tumor models. Unexpectedly, anti-VEGFR2, but not anti-VEGFR1, treatment completely blocked VEGF-induced anemia and BMC mobilization. Genetic deletion of Vegfr2 in endothelial cells markedly ablated VEGF-stimulated BMC mobilization. Conversely, deletion of the tyrosine kinase domain from Vegfr1 gene (Vegfr1TK−/−) did not affect VEGF-induced BMC mobilization. Analysis of VEGFR1+/VEGFR2+ populations in peripheral blood and BM showed no significant ratio difference between VEGF- and control tumor-bearing animals. These findings demonstrate that vascular dilation through the VEGFR2 signaling is the mechanism underlying VEGF-induced BM mobilization and anemia. Thus, our data provide mechanistic insights on VEGF-induced BMC mobilization in tumors and have therapeutic implications by targeting VEGFR2 for cancer therapy.
DOI Link: 10.1016/j.celrep.2014.09.003
ISSN: 2211-1247
eISSN: 2211-1247
Links: http://www.sciencedirect.com/science/article/pii/S2211124714007712
http://hdl.handle.net/2381/31883
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/) DOI: 10.1016/j.celrep.2014.09.003
Description: Supplemental materials at: Document S1. Supplemental Experimental Procedures and Figures S1–S5. http://www.sciencedirect.com/science/MiamiMultiMediaURL/1-s2.0-S2211124714007712/1-s2.0-S2211124714007712-mmc1.pdf/280959/FULL/S2211124714007712/fc714754e08d8a44f5c473c0afb58d19/mmc1.pdf and Document S2. Article plus Supplemental Information. http://www.sciencedirect.com/science/MiamiMultiMediaURL/1-s2.0-S2211124714007712/1-s2.0-S2211124714007712-mmc2.pdf/280959/FULL/S2211124714007712/71e9db57318036cf22be437be66e29a2/mmc2.pdf?_role=article-plus
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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