Hypoxia appears to induce a program which shifts the cellular phenotype toward an increase in extracellular adenosine. Hypoxia-inducible factor-1 (HIF-1) is a key regulator of genes crucial to many aspects of cancer biology. Since in gliomas there is a strong correlation between HIF-1 alpha expression, tumor grade and tumor vascularization, the aim of this study was to investigate whether adenosine may regulate HIF-1 in human glioblastoma cell lines. The results indicate that in the human hypoxic A172 and U87MG glioblastoma. cell lines adenosine up-regulates HIF-1 alpha protein expression via the A(3) receptor subtype. In particular, we investigated the effect of A(3) receptor antagonists on HIF-1 and vascular endothelial growth factor (VEGF) expression. We found that A(3) antagonists inhibit adenosine-induced HIF-1 alpha and VEGF protein accumulation in the hypoxic cells. Investigations in the molecular mechanism showed that A(3) receptor stimulation activates p44/p42 and p38 MAPKs that are required for A(3)-induced increase of HIF-1 alpha and VEGF. Further studies are required to demonstrate the in vivo relevance of these observations with regard to the proposed role for adenosine as a key element in hypoxia and in tumors.

Adenosine modulates vascular endothelial growth factor expression via hypoxia-inducible factor-1 in human glioblastoma cells / Merighi, S.; Benini, A.; Mirandola, Prisco; Gessi, S.; Varani, K.; Leung, E.; Maclennan, S.; Borea, P. A.. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 0006-2952. - 72:(2006), pp. 19-31. [10.1016/j.bcp.2006.03.020]

Adenosine modulates vascular endothelial growth factor expression via hypoxia-inducible factor-1 in human glioblastoma cells

MIRANDOLA, Prisco;
2006-01-01

Abstract

Hypoxia appears to induce a program which shifts the cellular phenotype toward an increase in extracellular adenosine. Hypoxia-inducible factor-1 (HIF-1) is a key regulator of genes crucial to many aspects of cancer biology. Since in gliomas there is a strong correlation between HIF-1 alpha expression, tumor grade and tumor vascularization, the aim of this study was to investigate whether adenosine may regulate HIF-1 in human glioblastoma cell lines. The results indicate that in the human hypoxic A172 and U87MG glioblastoma. cell lines adenosine up-regulates HIF-1 alpha protein expression via the A(3) receptor subtype. In particular, we investigated the effect of A(3) receptor antagonists on HIF-1 and vascular endothelial growth factor (VEGF) expression. We found that A(3) antagonists inhibit adenosine-induced HIF-1 alpha and VEGF protein accumulation in the hypoxic cells. Investigations in the molecular mechanism showed that A(3) receptor stimulation activates p44/p42 and p38 MAPKs that are required for A(3)-induced increase of HIF-1 alpha and VEGF. Further studies are required to demonstrate the in vivo relevance of these observations with regard to the proposed role for adenosine as a key element in hypoxia and in tumors.
2006
Adenosine modulates vascular endothelial growth factor expression via hypoxia-inducible factor-1 in human glioblastoma cells / Merighi, S.; Benini, A.; Mirandola, Prisco; Gessi, S.; Varani, K.; Leung, E.; Maclennan, S.; Borea, P. A.. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 0006-2952. - 72:(2006), pp. 19-31. [10.1016/j.bcp.2006.03.020]
File in questo prodotto:
File Dimensione Formato  
Biochem2006.pdf

non disponibili

Tipologia: Documento in Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 1.29 MB
Formato Adobe PDF
1.29 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2407955
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 115
  • ???jsp.display-item.citation.isi??? 105
social impact