Metabolomic profile and fractal dimensions in breast cancer cells

During the last decades compelling evidence has accumulated indicating that abnormalities in metabolism of cancer cells could play a strategic role in tumour initiation and behaviour. Abnormalities in metabolism are likely a consequence of several alterations in the complex network of signal transduction pathways, which may be caused by both genetic and epigenetic factors. An aberrant energy metabolism was recognized as one of the prominent features of the malignant phenotype, since the pioneering work of Warburg. It is now well established that the majority of tumours is characterized by a high glucose consumption, even under aerobic conditions, in absence of the Pasteur Effect, i.e. the lack of inhibition of glycolysis when cancer cells are exposed to normal oxygen consumption. Several investigators provided experimental data in support of a specific structure of the metabolic network in cancer cells. The 'tumour metabolome' has been defined as the metabolic tumour profile characterized by high glycolytic and glutaminolytic capacity and a high channelling of glucose carbons toward synthetic processes. Despite no archetypal cancer cell genotype exists, facing the wide genotypic heterogeneity of each tumour cell population, some malignant features (i.e. invasion, uncontrolled growth, apoptosis inhibition, metastasis spreading) are virtually shared by all cancers. This paradox of a common clinical behaviour despite marked both genotypic and epigenetic diversity needs to be investigated by a Systems Biology approach and suggests that cancer phenotype should be considered as a sort of "attractor" in a specific space phase defined by thermodynamic and kinetic constraints. This is not the only phase space cancer cells are embedded into: in principle cancer cells, like any living entity travel along an integrated set of genetic, epigenetic or metabolomic parameters. A fractal dimension formalism can be used in a prospective reconstruction of cancer attractors. Studies conducted on MCF-7 and MDA-MB-231 breast cancer cells, exposed to different morphogenetic fields, show that metabolomic profile correlates to cell shape: modification of cell shape and/or architectural characteristics of the cancer-tissue relationships, induced through manipulation of environmental cues, are followed by significant modification of the cancer metabolome as well as of the fractal dimensions at both single cell and cell population level. These results suggest how metabolomic shifts in cancer cells need to be considered as an adaptive modification adopted by a complex system under environmental constraints defined by the non-linear thermodynamic of the specific attractor occupied by the system. Indeed, characterization of cancer cells behaviour by means of both metabolomic and fractal parameters could be used to build an operational and meaningful space phase, that could help in evidencing the transitions boundaries as well as the singularities of cancer behaviour. Hence, by revealing tumour-specific metabolic shifts in tumour cells, metabolic profiling enables drug developers to identify the metabolic steps that control cell proliferation, thus aiding the identification of new anti-cancer targets and screening of lead compounds for antiproliferative metabolic effects. © 2011 by Nova Science Publishers, Inc. All rights reserved.