Norbert W. Lutz1, Johanna Chiche2,
Yann Le Fur1, Christophe Vilmen1, Frdric Frassineti3,
Laurent Daniel3, Jacques Pouyssgur2, Patrick J.
Cozzone1
1CRMBM UMR 6612 CNRS, Aix-Marseille
University, Medical School, Marseille, PACA, France; 2Institute of
Developmental Biology and Cancer Research CNRS UMR 6543, Centre A.
Lacassagne, Nice; 3Inserm UMR 911-CRO2, Aix-Marseille University,
Medical School
The
current use of angiogenesis inhibitors for cancer treatment requires further
modifications of the hypoxic tumor microenvironment to achieve complete tumor
regression. To contribute to the
development of a new treatment strategy, we investigated effects of
modulations of multiple mechanisms of glycolytic activity and pH regulation
on intracellular and extracellular pH (pHi, pHe) by 31P
NMR spectroscopy of tumor xenografts in nude mice. Three ras-transformed
fibroblast variants were compared: wild-type CCL39, and mutants defective in
either glycolysis or respiration. Compared to CCL39, pHi was
increased in either mutant, and pHe was less heterogenous due to a
reduction of low-pHe regions.
Keywords