Acute L-glutamine deprivation compromises VEGF-a upregulation in A549/8 human carcinoma cells

✍ Scribed by Benjamin Drogat; Marion Bouchecareilh; Sophie North; Cyril Petibois; Gérard Déléris; Eric Chevet; Andréas Bikfalvi; Michel Moenner

• Book ID: 102312628
• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 355 KB
• Volume: 212
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.21044

✦ Synopsis

Abstract

Tumor ischemia participates in angiogenesis and cancer progression through cellular responses to hypoxia and nutrient deprivation. However, the contribution of amino acids limitation to this process remains poorly understood. Using serum‐free cell culture conditions, we tested the impact of L‐glutamine deprivation on metabolic and angiogenic responses in A549/8 carcinoma cells. In these cells, lowering glutamine concentration modified the cell cycle distribution and significantly induced apoptosis/necrosis. Although glutamine deprivation led to a HIF‐independent increase in VEGF‐A mRNA, the corresponding protein level remained low and correlated with the inhibition of protein synthesis and activation of the GCN2/eIF2α pathway. Limitation of glutamine availability also hampers hypoxia‐ and hypoglycemia‐induced VEGF‐A protein upregulation. Thus, glutamine deprivation may have no direct effect on VEGF‐dependent angiogenesis, compared to hypoxia or to glucose deprivation, and may instead be detrimental to cancer progression by antagonizing ischemia‐induced stresses. J. Cell. Physiol. 212: 463–472, 2007. © 2007 Wiley‐Liss, Inc.