Title: Impeding Macrophage Entry into Hypoxic Tumor Areas by Sema3A/Nrp1 Signaling Blockade Inhibits Angiogenesis and Restores Antitumor Immunity
Authors: Casazza, Andrea ×
Laoui, Damya
Wenes, Mathias
Rizzolio, Sabrina
Bassani, Nicklas
Mambretti, Marco
Deschoemaeker, Sofie
Van Ginderachter, Jo A
Tamagnone, Luca
Mazzone, Max #
Issue Date: Dec-2013
Publisher: Cell Press
Series Title: Cancer Cell vol:24 issue:6 pages:695-709
Article number: 10.1016/j.ccr.2013.11.007
Abstract: Recruitment of tumor-associated macrophages (TAMs) into avascular areas sustains tumor progression; however, the underlying guidance mechanisms are unknown. Here, we report that hypoxia-induced Semaphorin 3A (Sema3A) acts as an attractant for TAMs by triggering vascular endothelial growth factor receptor 1 phosphorylation through the associated holoreceptor, composed of Neuropilin-1 (Nrp1) and PlexinA1/PlexinA4. Importantly, whereas Nrp1 levels are downregulated in the hypoxic environment, Sema3A continues to regulate TAMs in an Nrp1-independent manner by eliciting PlexinA1/PlexinA4-mediated stop signals, which retain them inside the hypoxic niche. Consistently, gene deletion of Nrp1 in macrophages favors TAMs' entrapment in normoxic tumor regions, which abates their pro-angiogenic and immunosuppressive functions, hence inhibiting tumor growth and metastasis. This study shows that TAMs' heterogeneity depends on their localization, which is tightly controlled by Sema3A/Nrp1 signaling.
ISSN: 1535-6108
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Tumor Inflammation and Angiogenesis (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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