Adam Meadows.

Graduate Student
University of California, Berkeley

B.S. Chemical Engineering, 2001
Purdue University

Co-Advisor: Harvey Blanch, Ph.D.
Office Location: 497A Tan Hall
Office Telephone: 643-8340
Office Fax: 643-1228

Characterizing the cellular metabolism of cancerous and non-cancerous breast cells

My research has focused on characterizing the metabolism of a human breast cancer cell line (MCF7) and comparing it to the metabolism of a normal breast cell line (48R HMEC, courtesy of Dr. Martha Stampfer’s Laboratory). Because the somatic evolution of breast cancer typically involves passage through a nutrient deprived, high-cell density metabolic bottle neck associated with a tumor, we hypothesize that there might be some persistent metabolic alterations within cancer cells that arose during adaptation to this environment. For example, cancer cells often convert a substantial fraction of their primary carbon source (glucose) to lactate under all conditions, despite its inherent metabolic inefficiency under oxygenated conditions. Indeed, one of the most common means of imaging a tumor non-invasively is via positron emission tomography, or PET. This technique exploits the high uptake rate of glucose by tumor cells, by feeding a radioactive form of glucose which is selectively enriched in tumor regions. Quantifying the metabolic differences between breast cancer and normal cells under going “wound repair” would reveal what metabolic program the tumor environment has selected for in cancer cells, while controlling for metabolic rates that are simply a result of a heightened growth rate. Furthermore, from a treatment perspective, the unique metabolism that sustained the cancer cells within the tumor might be used as a means of identifying and/or selectively targeting the offending population of cancerous cells.

The primary goal of my research is to develop high resolution metabolic profiles associated with a rapid growth in both cell lines. Our experimental approach involves manipulating the growth conditions such that the rate of mass replication is approximately equal in both cell lines. Cells were grown in the presence of a 13C-labeled substrate and allowed to reach a metabolic and isotopic steady state. Subsequent 13C-NMR and GC-MS measurements of cellular metabolites were able to determine the distribution of isotope within cellular biomass. Labeling information is extremely valuable when interpreted within the framework of metabolic flux analysis (MFA). MFA is a highly developed method of quantifying an entire system of intracellular fluxes within a metabolic network. Although traditionally applied towards anchorage-free prokaryotic organisms growing in chemostats, we have successfully adapted the methodology to anchorage-dependent human cells. A cellular automaton computer simulation was developed to optimally design these experiments.

Our initial results have provided some useful insights into the similarities and differences between the two cell lines. For example, both cell lines exhibited high glycolytic fluxes, although, surprisingly, the cancer cells had lower rates of glucose consumption per cell than did the normal cells. This result is unexpected given that aerobic glycolysis is one of the metabolic hallmarks of cancer cells in vivo. However, given the nutrient deprived environment of a tumor, higher metabolic efficiency, defined here as the yield of cells per mole of nutrient consumed, might be a necessary and advantageous adaptation for survival.