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Abstract #0557

Genetic Manipulation of Proton Transport Mechanisms Generates Modulations of Intra & Extracellular Ph & Growth Characteristics in Tumors

Norbert W. Lutz1, Johanna Chiche2, Yann LeFur1, Frederic Frassineti3, Laurent Daniel3, Jacques Pouyssegur2, Patrick J. Cozzone1

1Dept. of Medicine La Timone, Marseille, France; 2Institute of Developmental Biology & Cancer, University of Nice, Nice, France; 3Dept. of Pathology La Timone, Marseille, France

The excessive production of lactic acid through glycolysis in tumors can in principle be exploited for cancer treatment by using drugs to decrease intracellular pH (pHi), thus inducing cell death. We now present results obtained for fibroblasts genetically manipulated to modulate two proton transport mechanisms, the sodium/proton exchanger, NHE1, and the monocarboxylate transporter, MCT4. pHi and extracellular pH (pHe) were determined simultaneously in vivo in a nude mouse model, in conjunction with tumor morphology, tumor growth and necrosis, and were complemented with histological data. Our results validate the suggested treatment concept based on manipulating pH regulation via MCT4 and NHE1.