Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages

Jose Rafael Sierra, Simona Corso, Luisa Caione, Virna Cepero, Paolo Conrotto, Alessandro Cignetti, Wanda Piacibello, Atsushi Kumanogoh, Hitoshi Kikutani, Paolo Maria Comoglio, Luca Tamagnone, Silvia Giordano

Research output: Contribution to journalArticlepeer-review


Increased evidence suggests that cancer-associated infiammation 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 infiammatory cells of the tumor stroma and leads to the identification of an angiogenic molecule that might be a novel therapeutic target.

Original languageEnglish
Pages (from-to)1673-1685
Number of pages13
JournalJournal of Experimental Medicine
Issue number7
Publication statusPublished - Jul 7 2008

ASJC Scopus subject areas

  • Immunology


Dive into the research topics of 'Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages'. Together they form a unique fingerprint.

Cite this