Editors' ChoiceCancer

Distinct nutrient use in tumors

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Science Signaling  18 May 2021:
Vol. 14, Issue 683, eabj4738
DOI: 10.1126/scisignal.abj4738

Tumor cells and immune cells in the tumor microenvironment differentially take up nutrients.

Cancer cells in the tumor microenvironment (TME) metabolize glucose through aerobic glycolysis (Warburg metabolism) to support their proliferation. Tumor-infiltrating immune cells, including macrophages and T cells, also rely on glucose. Given that glucose uptake can be monitored by PET imaging, which is used to detect and monitor tumors, Reinfeld et al. used PET to analyze human tumors and mouse tumors from various models. The authors found that glucose was preferentially taken up by immune cells rather than tumor cells in the TME and to a greater extent by myeloid cells than by T cells. Signaling by mTORC1 supports nutrient uptake. Inhibition of mTORC1 with rapamycin led to decreased glucose uptake and metabolism in tumor myeloid cells without affecting those in tumor cells or T cells. Further PET analysis showed that, compared to tumor immune cells, tumor cells showed increased uptake of glutamine, an amino acid that is essential for many types of cancer. Treatment of tumor-bearing mice with an inhibitor of glutamine transport led to decreased glutamine uptake, but increased glucose uptake by tumor cells in the TME, suggesting that glutamine metabolism suppresses glucose metabolism in tumors. Together, these findings suggest that distinct cell types within the TME preferentially consume distinct nutrients from the common pool, that these preferences are cell-intrinsic, and that glucose uptake is modulated by glutamine uptake. Thus, the authors suggest that targeting glutamine uptake could be used to disrupt tumor cell metabolism and alter cell activities within the TME.

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