The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Impeding Macrophage Entry into Hypoxic Tumor Areas by Sema3A/Nrp1 Signaling Blockade Inhibits Angiogenesis and Restores Antitumor Immunity
Open accessAbstract
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.
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Cites
Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm
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Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes
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Self-citationNeuropilin Is a Semaphorin III Receptor
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Cited by
Microenvironmental regulation of tumour angiogenesis
De Palma, M., Biziato, D., & Petrova, T. V. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.51 · Cited by 1,847
Hypoxia and the extracellular matrix: drivers of tumour metastasis
Gilkes, D. M., Semenza, G. L., & Wirtz, D. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3726 · Cited by 1,520
Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment
Chanmee, T., Ontong, P., Konno, K., & Itano, N. (2014) · Cancers · doi:10.3390/cancers6031670 · Cited by 1,538
Macrophages and Therapeutic Resistance in Cancer
Ruffell, B., & Coussens, L. M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.02.015 · Cited by 1,474
HIF transcription factors, inflammation, and immunity
Palazon, A., Goldrath, A. W., Nizet, V., & Johnson, R. S. (2014) · Immunity · doi:10.1016/j.immuni.2014.09.008 · Cited by 1,195
Metadata
- Authors
- Casazza, A., Laoui, D., Wenes, M., Rizzolio, S., Bassani, N., Mambretti, M., Deschoemaeker, S., Van Ginderachter, J. A., Tamagnone, L., & Mazzone, M.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 24
- Issue
- 6
- Pages
- 695-709
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2165036434
- Cited by
- 629
- References
- 53
- FWCI
- 17.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Casazza, A., Laoui, D., Wenes, M., Rizzolio, S., Bassani, N., Mambretti, M., Deschoemaeker, S., Van Ginderachter, J. A., Tamagnone, L., & Mazzone, M. (2013). Impeding Macrophage Entry into Hypoxic Tumor Areas by Sema3A/Nrp1 Signaling Blockade Inhibits Angiogenesis and Restores Antitumor Immunity. Cancer Cell. https://doi.org/10.1016/j.ccr.2013.11.007
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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