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Colla, Simona; Tagliaferri, Sara; Morandi, Francesca; Lunghi, Paolo; Donofrio, Gaetano; Martorana, Davide; Mancini, Cristina; Lazzaretti, Mirca; Mazzera, Laura; Ravanetti, Lara; Bonomini, Sabrina; Ferrari, Luca; Miranda, Claudia; Ladetto, Marco; Neri, Tauro Maria; Neri, Antonino; Greco, Angela; Mangoni, Marcellina; Bonati, Antonio; Rizzoli, Vittorio; Giuliani, Nicola

The new tumor-suppressor gene inhibitor of growth family member 4 (ING4) regulates the production of proangiogenic molecules by myeloma cells and suppresses hypoxia-inducible factor-1 α (HIF-1α) activity: involvement in myeloma-induced angiogenesis

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  • Medientyp: E-Artikel
  • Titel: The new tumor-suppressor gene inhibitor of growth family member 4 (ING4) regulates the production of proangiogenic molecules by myeloma cells and suppresses hypoxia-inducible factor-1 α (HIF-1α) activity: involvement in myeloma-induced angiogenesis
  • Beteiligte: Colla, Simona; Tagliaferri, Sara; Morandi, Francesca; Lunghi, Paolo; Donofrio, Gaetano; Martorana, Davide; Mancini, Cristina; Lazzaretti, Mirca; Mazzera, Laura; Ravanetti, Lara; Bonomini, Sabrina; Ferrari, Luca; Miranda, Claudia; Ladetto, Marco; Neri, Tauro Maria; Neri, Antonino; Greco, Angela; Mangoni, Marcellina; Bonati, Antonio; Rizzoli, Vittorio; Giuliani, Nicola
  • Erschienen: American Society of Hematology, 2007
  • Erschienen in: Blood, 110 (2007) 13, Seite 4464-4475
  • Sprache: Englisch
  • DOI: 10.1182/blood-2007-02-074617
  • ISSN: 0006-4971; 1528-0020
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: Angiogenesis has a critical role in the pathophysiology of multiple myeloma (MM); however, the molecular mechanisms underlying this process are not completely elucidated. The new tumor-suppressor gene inhibitor of growth family member 4 (ING4) has been recently implicated in solid tumors as a repressor of angiogenesis. In this study, we found that ING4 expression in MM cells was correlated with the expression of the proangiogenic molecules interleukin-8 (IL-8) and osteopontin (OPN). Moreover, we demonstrate that ING4 suppression in MM cells up-regulated IL-8 and OPN, increasing the hypoxia inducible factor-1α (HIF-1α) activity and its target gene NIP-3 expression in hypoxic condition. In turn, we show that the inhibition of HIF-1α by siRNA suppressed IL-8 and OPN production by MM cells under hypoxia. A direct interaction between ING4 and the HIF prolyl hydroxylase 2 (HPH-2) was also demonstrated. Finally, we show that ING4 suppression in MM cells significantly increased vessel formation in vitro, blunted by blocking IL-8 or OPN. These in vitro observations were confirmed in vivo by finding that MM patients with high IL-8 production and microvascular density (MVD) have significantly lower ING4 levels compared with those with low IL-8 and MVD. Our data indicate that ING4 exerts an inhibitory effect on the production of proangiogenic molecules and consequently on MM-induced angiogenesis.
  • Zugangsstatus: Freier Zugang