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Dis Model Mech. 2018 Aug 7;11(8). pii: dmm035758. doi: 10.1242/dmm.035758.

Microenvironmental regulation of cancer cell metabolism: implications for experimental design and translational studies.

Author information

1
Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA mvh@mit.edu muir.alexander@gmail.com.
2
Department of Biochemistry and Molecular Biology, University of Massachusetts Amherst, Amherst, MA 01003, USA.
3
Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Abstract

Cancers have an altered metabolism, and there is interest in understanding precisely how oncogenic transformation alters cellular metabolism and how these metabolic alterations can translate into therapeutic opportunities. Researchers are developing increasingly powerful experimental techniques to study cellular metabolism, and these techniques have allowed for the analysis of cancer cell metabolism, both in tumors and in ex vivo cancer models. These analyses show that, while factors intrinsic to cancer cells such as oncogenic mutations, alter cellular metabolism, cell-extrinsic microenvironmental factors also substantially contribute to the metabolic phenotype of cancer cells. These findings highlight that microenvironmental factors within the tumor, such as nutrient availability, physical properties of the extracellular matrix, and interactions with stromal cells, can influence the metabolic phenotype of cancer cells and might ultimately dictate the response to metabolically targeted therapies. In an effort to better understand and target cancer metabolism, this Review focuses on the experimental evidence that microenvironmental factors regulate tumor metabolism, and on the implications of these findings for choosing appropriate model systems and experimental approaches.

KEYWORDS:

Cancer; Cancer models; Metabolism; Microenvironment; Nutrient availability; Nutrient sensing

PMID:
30104199
PMCID:
PMC6124553
DOI:
10.1242/dmm.035758
[Indexed for MEDLINE]
Free PMC Article

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