Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Department of Biochemistry and Molecular Biology, University of Massachusetts Amherst, Amherst, MA 01003, USA.
Dis Model Mech. 2018 Aug 7;11(8):dmm035758. doi: 10.1242/dmm.035758.
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 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.
癌症具有改变的代谢，人们有兴趣准确地了解致癌转化如何改变细胞代谢，以及这些代谢改变如何转化为治疗机会。研究人员正在开发越来越强大的实验技术来研究细胞代谢，这些技术允许分析肿瘤和癌症模型中的癌细胞代谢。这些分析表明，虽然癌细胞内在的因素，如致癌突变，改变了细胞代谢，但细胞外在的微环境因素也对癌细胞的代谢表型有很大的贡献。这些发现强调了肿瘤内的微环境因素，如营养物质的可用性、细胞外基质的物理性质以及与基质细胞的相互作用，可以影响癌细胞的代谢表型，并最终决定对代谢靶向治疗的反应。为了更好地理解和靶向癌症代谢，本综述重点介绍了微环境因素调节肿瘤代谢的实验证据，以及这些发现对选择合适的模型系统和实验方法的影响。
