Many cancer therapeutics have been targeted toward enzymes in the polyamine ABT metabolism pathway, with promising initial results. Proline has recently been shown to induce differentiation in mESCs towards an epiblast stem cell state, induced by catabolism of proline to pyrroline-5-carboxylate. In addition, proline has been suggested to act as a signaling molecule that controls stem cell behavior. Putrescine has long been known to promote differentiation, as have other polyamines. Polyamines were found to be statistically significantly reduced in induced pluripotent stem cells compared to fibroblasts, suggesting potential involvement of polyamine metabolism in reprogramming for stem-like phenotypes. This evidence together suggests the possibility that the levels of proline and putrescine, while each implicated in cancer, may play additional roles in the stem-like state of OCSCs; specifically, maintenance of one or both of these molecules at lower levels may help to maintain the stem-like state of OCSCs, consistent with ideas proposed elsewhere about the interplay between metabolism and cancer stemness. Additional detailed experiments are necessary to investigate this hypothesis. An interesting picture emerges when differences in metabolite abundances between OCCs and OCSCs are compared with differences in metabolite abundances between ovarian borderline tumors and invasive ovarian carcinomas.While tissue concentrations of glycine, proline, glutamate, and fumarate are higher in invasive ovarian carcinomas relative to non-invasive borderline tumors, our data show that OCSCs display lower concentrations of these metabolites relative to OCCs. Glycine plays a role in rapid proliferation of cancer cells via de novo purine synthesis and the SOG pathway. The SOG pathway consists of serine synthesis, one-carbon metabolism, and the glycine cleavage system and supports rapid proliferation through energy production. Considering the role of glycine in rapid proliferation of cancer cells, the role of fumarate in the malignant phenotype via aberrant activation of hypoxia response pathways, and the role of glutamate in anabolic processes and replenishing of the A 77636 hydrochloride tricarboxylic acid cycle intermediates during cell growth, it is somewhat intriguing that OCSCs are metabolically more similar to indolent and relatively benign borderline tumor cells with respect to these cancer-relevant metabolites.We hypothesize that certain phenotypic similarities between cancer stem cells and cells with less malignant potential, might be associated with quiescence of these cell types and might play an important role in failure of cancer therapies designed to target aggressively growing clinical cancers. Similarly, our results imply that OCSCs may be less dependent on polyamines than their more differentiated progeny, which could be a more broadly applicable property of quiescent cancer stem cells that can explain the general failure of inhibitors of polyamine synthesis in clinical cancer trials.