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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3321-3329. Prepublished online as a Blood First Edition Paper on December 27, 2005; DOI 10.1182/blood-2005-06-2445. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-06-2445v1 107/8/3321    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Catalano, A. Articles by Procopio, A. Search for Related Content PubMed PubMed Citation Articles by Catalano, A. Articles by Procopio, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 20, 2005 Accepted December 5, 2005 Semaphorin-3A is expressed by tumor cells and alters T cell signal transduction and function Alfonso Catalano*, Paola Caprari, Simona Moretti, Monica Faronato, Luca Tamagnone, and Antonio Procopio Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Ancona, Italy; Center of Cytology, Italian National Research Centers on Aging (INRCA-IRCCS), Ancona, Italy Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Ancona, Italy; Neural Development Group, Mouse Cancer Genetics Program, National Cancer Institute, Frederick, Maryland, USA Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Ancona, Italy Institute for Cancer Research and Treatment, University of Turin, Candiolo, Italy * Corresponding author; email: catgfp{at}yahoo.it. An important aspect of tumor progression is the ability of cancer cells to escape detection and clearance by the immune system. Recent studies suggest that several tumors express soluble factors interfering with the immune response. Here, we show that semaphorin-3A (Sema-3A), a secreted member of the semaphorin family involved in axonal guidance, organogenesis and angiogenesis, is highly expressed in several tumor cells. Conditioned media of Sema-3A transfected COS-7 cells or human recombinant Sema-3A inhibited primary human T cell proliferation and cytokines production under anti-CD3 plus anti-CD28 stimulating conditions. Sema-3A also inhibited the activation of non-specific cytotoxic activity in MLC, as measured against K-562 cells. In contrast, suppression of Sema-3A in tumor cells with a small interfering RNA (siRNA) augmented T cell activation. The inhibitory effect of Sema-3A in T cells is mediated by blockade of Ras/mitogen-activated protein kinase (MAPK) signaling pathway. The presence of Sema-3A increased the activation of the Ras family small GTPase Rap1 and introduction of the dominant negative mutant of Rap1 (Rap1N17) blunted the immuno-inhibitory effects of Sema-3A. These results suggest that Sema-3A inhibits primary T cell activation and imply that it can contribute to the T cell dysfunction in the tumor microenvironment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Yamamoto, K. Suzuki, T. Okuno, T. Ogata, N. Takegahara, H. Takamatsu, M. Mizui, M. Taniguchi, A. Chedotal, F. Suto, et al. Plexin-A4 negatively regulates T lymphocyte responses Int. Immunol., March 1, 2008; 20(3): 413 - 420. [Abstract] [Full Text] [PDF] S. Moretti, A. Procopio, R. Lazzarini, M. R. Rippo, R. Testa, M. Marra, L. Tamagnone, and A. Catalano Semaphorin3A signaling controls Fas (CD95)-mediated apoptosis by promoting Fas translocation into lipid rafts Blood, February 15, 2008; 111(4): 2290 - 2299. [Abstract] [Full Text] [PDF]

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