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Systemic and Target...
Systemic and Targeted Delivery of Semaphorin 3A Inhibits Tumor Angiogenesis and Progression in Mouse Tumor Models
- Article/chapterEnglish2011
Publisher, publication year, extent ...
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-151911
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-151911URI
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https://doi.org/10.1161/ATVBAHA.110.211920DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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. Conclusion-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.
Subject headings and genre
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angiogenesis
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molecular biology
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pathology
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receptors
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vascular biology
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metastasis
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neuropilin
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semaphorin
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tumor
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MEDICINE
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MEDICIN
Added entries (persons, corporate bodies, meetings, titles ...)
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Fu, XiUppsala universitet,Institutionen för immunologi, genetik och patologi
(author)
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Johansson, IrjaUppsala universitet,Institutionen för immunologi, genetik och patologi
(author)
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Capparuccia, Lorena
(author)
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Andersson, FredrikUppsala universitet,Institutionen för immunologi, genetik och patologi
(author)
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Giustacchini, Alice
(author)
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Squadrito, Mario Leonardo
(author)
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Venneri, Mary Anna
(author)
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Mazzone, Massimiliano
(author)
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Larsson, ErikUppsala universitet,Molekylär och morfologisk patologi(Swepub:uu)eriklars
(author)
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Carmeliet, Peter
(author)
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De Palma, Michele
(author)
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Naldini, Luigi
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Tamagnone, Luca
(author)
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Rolny, CharlotteUppsala universitet,Cancer och vaskulärbiologi
(author)
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Uppsala universitetInstitutionen för immunologi, genetik och patologi
(creator_code:org_t)
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Casazza, Andrea
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Uppsala University