oligomycins and Neoplasm-Metastasis

Gastric cancer is a leading cause of cancer death in many parts of the world. None of the tumor markers available to date provide for a reliable screening/diagnostic test. By using differential display technology on gastric cancer nonmetastatic (RF1) and metastatic (RF48) cell lines, we have isolated six novel cDNA clones. Five of them have not been previously identified. However, one of them appears to be the human homolog of the bovine oligomycin sensitivity conferral protein (oscp). Northern blot analysis showed that this clone is expressed at a much higher level in the metastatic (RF48) than the nonmetastatic (RF1) cancer cell line from the same patient. High level expression of the same gene is also observed in the breast cancer cell lines BT20 and T47D. The other five novel clones isolated showed either low or no expression in the RF1 and RF48 gastric cell lines, but variable levels of expression were detectable in breast cancers cell lines and normal tissues.

Topics: Adenosine Triphosphatases; Amino Acid Sequence; Animals; Base Sequence; Biomarkers, Tumor; Breast Neoplasms; Carrier Proteins; Cattle; DNA, Neoplasm; Humans; Membrane Proteins; Mitochondrial Proton-Translocating ATPases; Molecular Sequence Data; Neoplasm Metastasis; Oligomycins; Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms; Tumor Cells, Cultured

The energy requirements via glycolytic pathways were directly measured in migrating tumor cells. Motility in the metastatic human melanoma cell line A2058, stimulated by insulinlike growth factor I (IGF-I), depends on glycolysis in the presence of glucose as its principal source of energy. Motility in glucose-free medium was 75% reduced and utilized mitochondrial respiration (inhibited by oligomycin). With increasing (physiologic) glucose concentrations, there was a dramatic shift to anaerobic glycolysis as the energy source and 93% elimination of the oligomycin inhibition of motility. Oxamate, an inhibitor of glycolysis, inhibited motility at all glucose concentrations. CO2 production from glycolysis and from the hexose monophosphate shunt was measured in migrating tumor cells. The time course and glucose-dose dependence of glycolytic CO2 production correlated directly with motility. In contrast, mitochondrial CO2 production was inversely related to glucose concentration. A monoclonal antibody for the IGF-I receptor inhibited both motility and glycolytic CO2 production, indicating that both processes are receptor mediated.

Topics: Antibodies, Monoclonal; Chemotaxis; Cycloheximide; Energy Metabolism; Glucose; Glycolysis; Humans; In Vitro Techniques; Insulin-Like Growth Factor I; Melanoma; Neoplasm Metastasis; Oligomycins; Oxamic Acid; Receptors, Cell Surface; Receptors, Somatomedin; Time Factors; Tumor Cells, Cultured