The genetic alterations associated with cell transformation are in large measure expressed in the metabolic phenotype as cancer cells proliferate and change their local environment, and prepare for metastasis. Qualitatively, the fundamental biochemistry of cancer cells is generally the same as in the untransformed cells, but the cancer cells produce a local environment, the TME, that is hostile to the stromal cells, and compete for nutrients. In order to proliferate, cells need sufficient nutrients, either those that cannot be made by the cells themselves, or must be made from simpler precursors. However, in solid tumors, the nutrient supply is often limiting given the potential for rapid proliferation, and the poor quality of the vasculature. Thus, cancer cells may employ a variety of strategies to obtain nutrients for survival, growth and metastasis. Although much has been learned using established cell lines in standard culture conditions, it is becoming clear from in vivo metabolic studies that this can also be misleading, and which nutrients are used for energy production versus building blocks for synthesis of macromolecules can vary greatly from tumor to tumor, and even within the same tumor. Here we review the operation of metabolic networks, and how recent understanding of nutrient supply in the TME and utilization are being revealed using stable isotope tracers in vivo as well as in vitro.
|Number of pages||14|
|Journal||Genes and Diseases|
|State||Published - Jun 2020|
Bibliographical noteFunding Information:
This work was supported in part by the Carmen L Buck Chair in Oncology (to ANL), the Edith D. Gardner Chair in Cancer Research (to TWMF) and funding from NIH 1P01CA163223-01A1 , 5P20GM121327 and P30CA177558 .
This work was supported in part by the Carmen L Buck Chair in Oncology (to ANL), the Edith D. Gardner Chair in Cancer Research (to TWMF) and funding from NIH 1P01CA163223-01A1, 5P20GM121327 and P30CA177558.
© 2019 Chongqing Medical University
- Cancer metabolism
- Metabolic flux
- Nutrient supply
- Stable isotope resolved metabolomics
- Tumor microenvironment
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology