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Overexpression of dimethylarginine dimethylaminohydrolase enhances tumour hypoxia: an insight into the relationship of hypoxia and angiogenesis In vivo

Kostourou, Vassiliki and Troy, Helen and Murray, Joanne F. and Cullis, Elizabeth R. and Whitley, Guy St.J. and Griffiths, John R. and Robinson, Simon (2004) Overexpression of dimethylarginine dimethylaminohydrolase enhances tumour hypoxia: an insight into the relationship of hypoxia and angiogenesis In vivo. NeoPlasia, 6 (4). pp. 401-411. ISSN 1522-8002

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Official URL: http://dx.doi.org/10.1593/neo.04109

Abstract

The oxygenation status of tumors derived from wildtype C6 glioma cells and clone D27 cells overexpressing dimethylarginine dimethylaminohydrolase (DDAH) was assessed in vivo using a variety of direct and indirect assays of hypoxia. Clone D27 tumors exhibit a more aggressive and better-vascularized phenotype compared to wild-type C6 gliomas. Immunohistochemical analyses using the 2-nitroimidazole hypoxia marker pimonidazole, fiber optic OxyLite measurements of tumor pO2, and localized 31P magnetic resonance spectroscopy measurements of tumor bioenergetic status and pH clearly demonstrated that the D27 tumors were more hypoxic compared to C6 wild type. In the tumor extracts, only glucose concentrations were significantly lower in the D27 tumors. Elevated Glut-1 expression, a reliable functional marker for hypoxia-inducible factor-1 - mediated metabolic adaptation, was observed in the D27 tumors. Together, the data show that overexpression of DDAH results in C6 gliomas that are more hypoxic compared to wild-type tumors, and point strongly to an inverse relationship of tumor oxygenation and angiogenesis in vivo - a concept now being supported by the enhanced understanding of oxygen sensing at the molecular level.

Item Type:Article
Additional Information:Online ISSN 1476-5586
Uncontrolled Keywords:Hypoxia, angiogenesis, DDAH, ADMA, nitric oxide
Research Community:University of Westminster > Life Sciences, School of
ID Code:1557
Deposited On:12 May 2006
Last Modified:11 Aug 2010 15:30

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