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. J. Leukoc. Biol. 87: 365-369; 2010.

Naldini, A., Morena, E., Pucci, A., Pellegrini, M., Baldari, C.T., Pelicci, P.G., et al. (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 [10.1189/jlb.0709460].

The adaptor protein p66Shc is a positive regulator in the angiogenic response induced by hypoxic T cells

NALDINI, A.;MORENA, E.;PUCCI, A.;BALDARI, C. T.;CARRARO, F.
2010-01-01

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. J. Leukoc. Biol. 87: 365-369; 2010.
Naldini, A., Morena, E., Pucci, A., Pellegrini, M., Baldari, C.T., Pelicci, P.G., et al. (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 [10.1189/jlb.0709460].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/23238
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