Genomic and phenomic correlations in the respiration of basal cell carcinomas

Early last century Warburg1 described differences in metabolism between normal and cancer cells, however subsequent research did not bear out what he considered to be the “primary cause of cancer,” i.e., the replacement of respiration by fermentation 2. Since then attention continues to periodically focus on analysis of the enzymology &/or energetics of oxygen metabolism in cancer cells. Despite such studies, there is still debate as to whether cancers shift towards aerobic metabolism or transform toward a more anaerobic metabolism3. While many theories were advanced to explain those findings, no consistent pattern emerged to correlate the changes observed across all cancers studied. Among many such studies was an investigation we carried out into the enzymology and isoenzymology of human non-melanotic skin cancers (NMSCs). In that research, the levels of three enzymes involved in glucose metabolism, namely lactate dehydrogenase (LDH), aldolase and glucose-6-phospshate dehydrogenase (G-6-PDH), were shown to be depressed in basal cell carcinoma tissue (BCC) compared to normal skin. By contrast, the level of another enzyme, NADP+-dependent isocitrate dehydrogenase was elevated. Those results confirmed the fmdings of Halprin’s group4. In further studies of the same material, the isoenzyme patterns of two of those enzymes were altered in BCC relative to normal skin. The changes seen in the LDH isoenzyme patterns, i.e. increases in the anionic species, were consistent with a shift to a more anaerobic metabolism as were the changes observed in aldolase. To further characterize the oxygen metabolism of BCC, the respiration of small volumes of tissue were directly measured using oxygen electrodes.