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Title: Systemic and Targeted Delivery of Semaphorin 3A Inhibits Tumor Angiogenesis and Progression in Mouse Tumor Models
Authors: Casazza, Andrea ×
Fu, Xi
Johansson, Irja
Capparuccia, Lorena
Andersson, Fredrik
Giustacchini, Alice
Squadrito, Mario Leonardo
Venneri, Mary Anna
Mazzone, Max
Larsson, Erik
Carmeliet, Peter
De Palma, Michele
Naldini, Luigi
Tamagnone, Luca
Rolny, Charlotte #
Issue Date: Jan-2011
Publisher: Lippincott, Williams & Wilkins
Series Title: Arteriosclerosis, Thrombosis and Vascular Biology vol:31 issue:4 pages:741-U55
Abstract: OBJECTIVE: The role of semaphorins in tumor progression is still poorly understood. In this study, we aimed at elucidating the regulatory role of semaphorin 3A (SEMA3A) in primary tumor growth and metastatic dissemination. METHODS AND RESULTS: We used 3 different experimental approaches in mouse tumor models: (1) overexpression of SEMA3A in tumor cells, (2) systemic expression of SEMA3A following liver gene transfer in mice, and (3) tumor-targeted release of SEMA3A using gene modified Tie2-expressing monocytes as delivery vehicles. In each of these experimental settings, SEMA3A efficiently inhibited tumor growth by inhibiting vessel function and increasing tumor hypoxia and necrosis, without promoting metastasis. We further show that the expression of the receptor neuropilin-1 in tumor cells is required for SEMA3A-dependent inhibition of tumor cell migration in vitro and metastatic spreading in vivo. CONCLUSIONS: In sum, both systemic and tumor-targeted delivery of SEMA3A inhibits tumor angiogenesis and tumor growth in multiple mouse models; moreover, SEMA3A inhibits the metastatic spreading from primary tumors. These data support the rationale for further investigation of SEMA3A as an anticancer molecule.
URI: 
ISSN: 1079-5642
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Laboratory of Tumor Inflammation and Angiogenesis (Vesalius Research Center) (+)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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