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PMID: 18559453 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of experimental medicine ·Vol. 205 ·No. 7 ·2008-07-07 ·Pages 1673-85

Sierra JR, Corso S, Caione L, Cepero V, Conrotto P, Cignetti A, Piacibello W, Kumanogoh A, Kikutani H, Comoglio PM, Tamagnone L, Giordano S

Abstract

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.

MeSH Terms
Angiogenesis Inducing Agents/metabolism Animals Cell Line Humans Inflammation/genetics,metabolism,pathology Macrophages/metabolism,pathology Mice Mice, Inbred BALB C Mice, Knockout Neoplasm Metastasis Neoplasms/genetics,metabolism,pathology Neovascularization, Pathologic/genetics,metabolism,pathology Nerve Tissue Proteins/genetics,metabolism Receptors, Cell Surface/genetics,metabolism Semaphorins/genetics,metabolism
Chemicals
Angiogenesis Inducing Agents Nerve Tissue Proteins Plxnb1 protein, mouse Receptors, Cell Surface Sema4d protein, mouse Semaphorins
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Sierra Jose Rafael
Institute for Cancer Research and Treatment, University of Torino Medical School, 10060 Candiolo, Torino, Italy.
Corso Simona
Caione Luisa
Cepero Virna
Conrotto Paolo
Cignetti Alessandro
Piacibello Wanda
Kumanogoh Atsushi
Kikutani Hitoshi
Comoglio Paolo Maria
Tamagnone Luca
Giordano Silvia
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
1540-9538
DOI
10.1084/jem.20072602
Published
2008-07-07
Epub
2008-00-16
Pages
1673-85
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2442644
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20072602 PMC Full Text View journal details
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