Systemic and targeted delivery of semaphorin 3A inhibits tumor angiogenesis and progression in mouse tumor models

Luca Tamagnone, Andrea Casazza, Xi Fu, Irja Johansson, Lorena Capparuccia, Fredrik Andersson, Alice Giustacchini, Mario Leonardo Squadrito, Mary Anna Venneri, Massimiliano Mazzone, Erik Larsson, Peter Carmeliet, Michele De Palma, Luigi Naldini, Charlotte Rolny

Risultato della ricerca: Contributo in rivistaArticolo in rivista

88 Citazioni (Scopus)

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. 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. © 2011 American Heart Association, Inc.
Lingua originaleEnglish
pagine (da-a)741-749
Numero di pagine9
RivistaArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
DOI
Stato di pubblicazionePubblicato - 2011

Keywords

  • Cardiology and Cardiovascular Medicine
  • angiogenesis
  • metastasis
  • molecular biology
  • neuropilin
  • pathology
  • receptors
  • semaphorin
  • tumor
  • vascular biology

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