Impact of metabolic heterogeneity on tumor growth, invasion, and treatment outcomes

Cancer Research
Mark Robertson-TessiAlexander R A Anderson

Abstract

Histopathologic knowledge that extensive heterogeneity exists between and within tumors has been confirmed and deepened recently by molecular studies. However, the impact of tumor heterogeneity on prognosis and treatment remains as poorly understood as ever. Using a hybrid multiscale mathematical model of tumor growth in vascularized tissue, we investigated the selection pressures exerted by spatial and temporal variations in tumor microenvironment and the resulting phenotypic adaptations. A key component of this model is normal and tumor metabolism and its interaction with microenvironmental factors. The metabolic phenotype of tumor cells is plastic, and microenvironmental selection leads to increased tumor glycolysis and decreased pH. Once this phenotype emerges, the tumor dramatically changes its behavior due to acid-mediated invasion, an effect that depends on both variations in the tumor cell phenotypes and their spatial distribution within the tumor. In early stages of growth, tumors are stratified, with the most aggressive cells developing within the interior of the tumor. These cells then grow to the edge of the tumor and invade into the normal tissue using acidosis. Simulations suggest that diffusible cytotoxic treatme...Continue Reading

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Related Concepts

Metabolic Process, Cellular
Study
Tumor Cells, Uncertain Whether Benign or Malignant
Exertion
Antibiotic Resistance, Neoplasm
Cytotoxicity Assay
Metabolic Networks and Pathways
Stratification
Neoplastic Cell
Acclimatization

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