Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages
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- Jose Rafael Sierra
- 1Institute for Cancer Research and Treatment, University of Torino Medical School, 10060 Candiolo (Torino), Italy
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- Simona Corso
- 1Institute for Cancer Research and Treatment, University of Torino Medical School, 10060 Candiolo (Torino), Italy
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- Luisa Caione
- 1Institute for Cancer Research and Treatment, University of Torino Medical School, 10060 Candiolo (Torino), Italy
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- Virna Cepero
- 1Institute for Cancer Research and Treatment, University of Torino Medical School, 10060 Candiolo (Torino), Italy
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- Paolo Conrotto
- 1Institute for Cancer Research and Treatment, University of Torino Medical School, 10060 Candiolo (Torino), Italy
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- Alessandro Cignetti
- 1Institute for Cancer Research and Treatment, University of Torino Medical School, 10060 Candiolo (Torino), Italy
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- Wanda Piacibello
- 1Institute for Cancer Research and Treatment, University of Torino Medical School, 10060 Candiolo (Torino), Italy
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- Atsushi Kumanogoh
- 2Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
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- Hitoshi Kikutani
- 2Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
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- Paolo Maria Comoglio
- 1Institute for Cancer Research and Treatment, University of Torino Medical School, 10060 Candiolo (Torino), Italy
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- Luca Tamagnone
- 1Institute for Cancer Research and Treatment, University of Torino Medical School, 10060 Candiolo (Torino), Italy
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- Silvia Giordano
- 1Institute for Cancer Research and Treatment, University of Torino Medical School, 10060 Candiolo (Torino), Italy
説明
<jats:p>Increased evidence suggests that cancer-associated inflammation supports tumor growth and progression. We have previously shown that semaphorin 4D (Sema4D), a ligand produced by different cell types, is a proangiogenic molecule that acts by binding to its receptor, plexin B1, expressed on endothelial cells (Conrotto, P., D. Valdembri, S. Corso, G. Serini, L. Tamagnone, P.M. Comoglio, F. Bussolino, and S. Giordano. 2005. Blood. 105:4321–4329). The present work highlights the role of Sema4D produced by the tumor microenvironment on neoplastic angiogenesis. We show that in an environment lacking Sema4D, the ability of cancer cells to generate tumor masses and metastases is severely impaired. This condition can be explained by a defective vascularization inside the tumor. We demonstrate that tumor-associated macrophages (TAMs) are the main cells producing Sema4D within the tumor stroma and that their ability to produce Sema4D is critical for tumor angiogenesis and vessel maturation. This study helps to explain the protumoral role of inflammatory cells of the tumor stroma and leads to the identification of an angiogenic molecule that might be a novel therapeutic target.</jats:p>
収録刊行物
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- The Journal of Experimental Medicine
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The Journal of Experimental Medicine 205 (7), 1673-1685, 2008-06-16
Rockefeller University Press