The adaptor protein p66shc is a positive regulator in the angiogenic response induced by hypoxic T cells

Antonella Naldini, Emilia Morena, Annalisa Pucci, Michela Pellegrini, Cosima T. Baldari, Pier Giuseppe Pelicci, Marco Presta, Domenico Ribatti, Fabio Carraro

Research output: Contribution to journalArticle

Abstract

Immune cells play an important role in the onset of angiogenesis. Here, we report that VEGF represents the major proangiogenic factor expressed by T cells exposed to hypoxia, a common feature of inflammation and tumor microenvironment. The supernatants of hypoxic T cells were highly angiogenic when delivered on the chick embryo CAM. The angiogenic response was abrogated by a neutralizing anti-VEGF antibody and mimicked by rVEGF. Interestingly, VEGF induction by hypoxia was up-regulated in Jurkat T cells overexpressing the adaptor protein p66Shc but not the inactive S36 p66Shc mutant, and it was abolished in p66Shc-/- mouse splenocytes. Accordingly, the angiogenic response induced by the supernatants from hypoxic p66Shc-/- splenocytes was reduced dramatically when compared with the wild-type controls. In conclusion, hypoxic T cells may contribute to the onset of angiogenesis through a novel VEGF-mediated mechanism, where p66Shc acts as a positive regulator.

Original languageEnglish
Pages (from-to)365-369
Number of pages5
JournalJournal of Leukocyte Biology
Volume87
Issue number3
DOIs
Publication statusPublished - Mar 2010

Keywords

  • Cytokines
  • Inflammation
  • T lymphocytes

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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    Naldini, A., Morena, E., Pucci, A., Pellegrini, M., Baldari, C. T., Pelicci, P. G., Presta, M., Ribatti, D., & Carraro, F. (2010). The adaptor protein p66shc is a positive regulator in the angiogenic response induced by hypoxic T cells. Journal of Leukocyte Biology, 87(3), 365-369. https://doi.org/10.1189/jlb.0709460