(447d) Ovarian Cancer Metabolomic Profiles Differ in Ovarian Cancer Initiating Cells

A key emerging area in cancer research is the study of stem-like “cancer initiating cells” (CICs) in tumor
populations. CICs are a major concern for effective cancer treatment, as they can self-renew, can
differentiate into cancer cells, and exhibit chemoresistance; they are thus suspected as a primary cause
of cancer recurrence. Very little is known about the molecular workings of these cells, and we must start
to understand them in order to effectively treat CICs. Metabolism is widely known to be dysfunctional
in cancer, most famously via the Warburg effect, but there is limited knowledge about CIC metabolism
and about cancer metabolism as a whole. Metabolomics is the study of cellular metabolism as a whole
by attempting to measure the levels of as many metabolites as possible. Metabolite levels integrate
the effects of gene regulation, environmental perturbations, and numerous other levels of regulation.
By profiling the metabolism over time, we can obtain a systems-level understanding of the metabolic
dynamics of CICs, which could profoundly affect our understanding, or even treatment, of cancer and
CICs.

Here we present the results of an in vitro glucose deprivation experiment to model in vivo tumor
conditions in ovarian cancer cells (OCCs) and ovarian CICs (OCICs). Extracellular and intracellular
metabolite samples were taken over a period of two days and were analyzed using two dimensional
gas chromatography – mass spectrometry (GCxGC-MS). To our knowledge, this is the first metabolic
profiling of OCIC metabolism. Distinct metabolic profiles were found for the two cell types and between
the control and glucose-deprived cells. Interestingly, independent of the differences imposed on the
cells by glucose deprivation, there is a characteristic set of intracellular metabolites that only appear in
OCCs, but not OCICs. These metabolites are spread across multiple pathways, suggesting system-wide
metabolic alteration of OCICs from OCCs and potentially serving as indicators of CIC transition or even
as therapeutic targets.