An altered metabolism during
ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of
cancer stem or tumor-initiating cells, small
tumor cell populations that are able to recapitulate the original
tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant,
MOSE-LFFLv (
TIC), derived from mouse ovarian surface epithelial (
MOSE) cells, to their parental (
MOSE-L) and benign precursor (
MOSE-E) cells.
TICs exhibit a decrease in
glucose and
fatty acid oxidation with a concomitant increase in
lactate secretion. In contrast to
MOSE-L cells,
TICs can increase their rate of glycolysis to overcome the inhibition of
ATP synthase by
oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign
MOSE-E cells.
TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with
AICAR, but exhibit a higher sensitivity to
metformin than
MOSE-E and
MOSE-L cells. Together, our data show that
TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current
therapy regimens to eradicate
TICs.