Expanding the Reach of Cancer Metabolomics

Abstract

Metabolism is again emerging as a key property that differentiates normal cells from neoplastic tissues. The coupling of this phenomenon with advanced bioanalytic methods may now open new avenues for diagnostics in cancer via discovery of chemical biomarkers. In this issue of Cancer Prevention Research, Montrose and colleagues apply metabolic profiling to a model of chemically induced colorectal cancer and describe the metabolomic landscape of colorectal tumors and associated biofluids in great detail. Their analysis of plasma and fecal metabolites provides inroads into the noninvasive detection of colorectal cancer using biochemical markers, as some conserved metabolic changes were altered across tumors, plasma, and feces. Meanwhile, the specific alterations identified in this study offer insights into potential metabolic drivers of colorectal cancer. For example, elevated sarcosine and 2-hydroxyglutarate were detected in these induced tumors, implicating their respective metabolic pathways and downstream interactions in colorectal cancer progression. This work highlights the potential value of cancer metabolomics for the noninvasive analysis of colorectal neoplasias while underscoring the importance of profiling diverse sample sets and metabolites in relevant cancer models to identify and validate such findings. Cancer Prev Res; 5(12); 1337-40. Ó2012 AACR.A complex set of integrated biochemical reactions are executed in our cells and tissues. This reaction network involves an extensive number of enzymes that interconvert diverse metabolites to carry out functions that include energy generation, biosynthesis, detoxification, protein modification, and the regulation of gene expression. As a result, our tissues harbor a complex profile of metabolites that is representative of biochemical network dynamics, and this metabolome fluctuates as a function of cellular phenotypes and tissue pathology. With the advent of new technologies that enable broad-spectrum quantitation of small molecules in cells and tissues, we are beginning to understand how changes in the metabolome correlate with specific diseases (1). In turn, this information may facilitate the discovery of potential biomarkers that can enable earlier prognoses in cancer or other diseases (2). Alternatively, these molecular signatures may provide mechanistic insights into potential therapies that target tumor metabolism (3). To accomplish these tasks, extensive analyses are required on the multitude of biologic samples available to clinicians in the hopes of identifying robust biomarkers with functional meaning.In this issue of Cancer Prevention Research, Montrose and colleagues profile the metabolome of azoxymethaneinduced colorectal tumors and characterize parallel changes in metabolite levels within plasma and fecal samples during cancer progression (4). These analyses enabled the identification of numerous metabolites that were consistently different in plasma and feces. Several of these markers overlapped with tumor samples as well. Levels of am...

Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health

“…Lactate is exported by MCTs which are also over-expressed in tumors (Halestrap, 2013). Moreover, glutamine sustains cytosolic citrate synthesis via IDH1 and lipogenesis (Metallo, 2012) (Figure 8). …”

Sarcosine as a Potential Prostate Cancer Biomarker—A Review

“…Metabolites play essential role in an understanding the biological reactions and thereby the changes in their levels contribute to the development of new diagnostic and therapeutic methods to diagnose specific diseases [46,47]. Biochemical pathways of formation and oxidation of sarcosine occur in mitochondria and are provided by two basic pathways (Figure 3).…”

“…This reaction forms dimethylglycine and regenerates methionine from homocysteine [44]. Dimethylglycine is subsequently converted to sarcosine via dimethylglycine dehydrogenase (DMGDH) [46,48]. The second metabolic pathway creates sarcosine during the transformation of the methyl group of S-adenosylmethionine catalysed by the enzyme glycine-N-methyltransferase (GNMT), that is a tetramer of identical 32 kDa subunits [49,50].…”

Loss of Merlin induces metabolomic adaptation that engages dependence on Hedgehog signaling

“…Recent advances have defined perspectives of metabolomic profiling of cancer that have defined treatment response, ‘stemness’, oxidative stress, changes with respect to the estrogen receptor (ER) status of breast cancer etc 171819…”