Impeding Macrophage Entry into Hypoxic Tumor Areas by Sema3A/Nrp1 Signaling Blockade Inhibits Angiogenesis and Restores Antitumor Immunity

Luca Tamagnone, Andrea Casazza, Damya Laoui, Mathias Wenes, Sabrina Rizzolio, Nicklas Bassani, Marco Mambretti, Sofie Deschoemaeker, Joa. Vanginderachter, Massimiliano Mazzone

Risultato della ricerca: Contributo in rivistaArticolo in rivista

307 Citazioni (Scopus)

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. © 2013 Elsevier Inc.
Lingua originaleEnglish
pagine (da-a)695-709
Numero di pagine15
RivistaCancer Cell
Volume24
DOI
Stato di pubblicazionePubblicato - 2013

Keywords

  • MACROPHAGES (TAMs)
  • NEUROPILIN-1
  • PLEXINA1/PLEXINA4
  • SEMA3A

Fingerprint

Entra nei temi di ricerca di 'Impeding Macrophage Entry into Hypoxic Tumor Areas by Sema3A/Nrp1 Signaling Blockade Inhibits Angiogenesis and Restores Antitumor Immunity'. Insieme formano una fingerprint unica.

Cita questo