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Citations to this article

Semaphorin 3A is an endogenous angiogenesis inhibitor that blocks tumor growth and normalizes tumor vasculature in transgenic mouse models
Federica Maione, … , Federico Bussolino, Enrico Giraudo
Federica Maione, … , Federico Bussolino, Enrico Giraudo
Published October 5, 2009
Citation Information: J Clin Invest. 2009;119(11):3356-3372. https://doi.org/10.1172/JCI36308.
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Research Article Oncology Article has an altmetric score of 4

Semaphorin 3A is an endogenous angiogenesis inhibitor that blocks tumor growth and normalizes tumor vasculature in transgenic mouse models

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Abstract

Tumor growth and progression rely upon angiogenesis, which is regulated by pro- and antiangiogenic factors, including members of the semaphorin family. By analyzing 3 different mouse models of multistep carcinogenesis, we show here that during angiogenesis, semaphorin 3A (Sema3A) is expressed in ECs, where it serves as an endogenous inhibitor of angiogenesis that is present in premalignant lesions and lost during tumor progression. Pharmacologic inhibition of endogenous Sema3A during the angiogenic switch, the point when pretumoral lesions initiate an angiogenic phase that persists throughout tumor growth, enhanced angiogenesis and accelerated tumor progression. By contrast, when, during the later stages of carcinogenesis following endogenous Sema3A downmodulation, Sema3A was ectopically reintroduced into islet cell tumors by somatic gene transfer, successive waves of apoptosis ensued, first in ECs and then in tumor cells, resulting in reduced vascular density and branching and inhibition of tumor growth and substantially extended survival. Further, long-term reexpression of Sema3A markedly improved pericyte coverage of tumor blood vessels, something that is thought to be a key property of tumor vessel normalization, and restored tissue normoxia. We conclude, therefore, that Sema3A is an endogenous and effective antiangiogenic agent that stably normalizes the tumor vasculature.

Authors

Federica Maione, Fabiola Molla, Claudia Meda, Roberto Latini, Lorena Zentilin, Mauro Giacca, Giorgio Seano, Guido Serini, Federico Bussolino, Enrico Giraudo

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2009 Total
Citations: 1 3 4 7 6 6 8 6 6 10 5 7 9 14 8 1 101
Citation information
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Citations to this article in year 2012 (14)

Title and authors Publication Year
Semaphorin 3A overcomes cancer hypoxia and metastatic dissemination induced by anti-angiogenic treatment in mice
Federica Maione, Stefania Capano, Donatella Regano, Lorena Zentilin, Mauro Giacca, Oriol Casanovas, Federico Bussolino, Guido Serini, Enrico Giraudo
Journal of Clinical Investigation 2012
Semaphorin 6A regulates angiogenesis by modulating VEGF signaling
M Segarra, H Ohnuki, D Maric, O Salvucci, X Hou, A Kumar, X Li, G Tosato
Blood 2012
Tumour growth inhibition and anti-metastatic activity of a mutated furin-resistant Semaphorin 3E isoform
A Casazza, B Kigel, F Maione, L Capparuccia, O Kessler, E Giraudo, M Mazzone, G Neufeld, L Tamagnone
EMBO Molecular Medicine 2012
Neuropilins: expression and roles in the epithelium
JR Wild, CA Staton, K Chapple, BM Corfe
International Journal of Experimental Pathology 2012
Vascular Normalization as a Therapeutic Strategy for Malignant and Nonmalignant Disease
S Goel, AH Wong, RK Jain
Cold Spring Harbor Perspectives in Medicine 2012
Semaphorins in Angiogenesis and Tumor Progression
G Neufeld, AD Sabag, N Rabinovicz, O Kessler
Cold Spring Harbor Perspectives in Medicine 2012
Recombinant Human Endostatin Normalizes Tumor Vasculature and Enhances Radiation Response in Xenografted Human Nasopharyngeal Carcinoma Models
F Peng, Z Xu, J Wang, Y Chen, Q Li, Y Zuo, J Chen, X Hu, Q Zhou, Y Wang, H Ma, Y Bao, M Chen
PloS one 2012
Semaphorin 3A Suppresses Tumor Growth and Metastasis in Mice Melanoma Model
G Chakraborty, S Kumar, R Mishra, TV Patil, GC Kundu
PloS one 2012
Semaphorin-3D and Semaphorin-3E Inhibit the Development of Tumors from Glioblastoma Cells Implanted in the Cortex of the Brain
AD Sabag, J Bode, D Fink, B Kigel, W Kugler, G Neufeld
PloS one 2012
Interplay of neuropilin-1 and semaphorin 3A after partial hepatectomy in rats
L Fu, T Kitamura, K Iwabuchi, S Ichinose, M Yanagida, H Ogawa, S Watanabe, T Maruyama, M Suyama, K Takamori
World journal of gastroenterology : WJG 2012
The VEGF Pathway in Cancer and Disease: Responses, Resistance, and the Path Forward
MW Kieran, R Kalluri, YJ Cho
Cold Spring Harbor Perspectives in Medicine 2012
Semaphorin3A, Neuropilin-1, and PlexinA1 Are Required for Lymphatic Valve Formation
K Bouvrée, I Brunet, R del Toro, E Gordon, C Prahst, B Cristofaro, T Mathivet, Y Xu, J Soueid, V Fortuna, N Miura, MS Aigrot, CH Maden, C Ruhrberg, JL Thomas, A Eichmann
Circulation research 2012
Double protection for weakened bones
M Zaidi, J Iqbal
Nature 2012
Merlin/NF2 regulates angiogenesis in schwannomas through a Rac1/semaphorin 3F-dependent mechanism.
Wong HK, Shimizu A, Kirkpatrick ND, Garkavtsev I, Chan AW, di Tomaso E, Klagsbrun M, Jain RK
Neoplasia (New York, N.Y.) 2012

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