[PDF][PDF] Isotope tracing in adult zebrafish reveals alanine cycling between melanoma and liver

FJ Naser, MM Jackstadt, R Fowle-Grider, JL Spalding… - Cell metabolism, 2021 - cell.com
FJ Naser, MM Jackstadt, R Fowle-Grider, JL Spalding, K Cho, E Stancliffe, SR Doonan…
Cell metabolism, 2021cell.com
The cell-intrinsic nature of tumor metabolism has become increasingly well characterized.
The impact that tumors have on systemic metabolism, however, has received less attention.
Here, we used adult zebrafish harboring BRAF V600E-driven melanoma to study the effect
of cancer on distant tissues. By applying metabolomics and isotope tracing, we found that
melanoma consume~ 15 times more glucose than other tissues measured. Despite this
burden, circulating glucose levels were maintained in disease animals by a tumor-liver …
Summary
The cell-intrinsic nature of tumor metabolism has become increasingly well characterized. The impact that tumors have on systemic metabolism, however, has received less attention. Here, we used adult zebrafish harboring BRAFV600E-driven melanoma to study the effect of cancer on distant tissues. By applying metabolomics and isotope tracing, we found that melanoma consume ~15 times more glucose than other tissues measured. Despite this burden, circulating glucose levels were maintained in disease animals by a tumor-liver alanine cycle. Excretion of glucose-derived alanine from tumors provided a source of carbon for hepatic gluconeogenesis and allowed tumors to remove excess nitrogen from branched-chain amino acid catabolism, which we found to be activated in zebrafish and human melanoma. Pharmacological inhibition of the tumor-liver alanine cycle in zebrafish reduced tumor burden. Our findings underscore the significance of metabolic crosstalk between tumors and distant tissues and establish the adult zebrafish as an attractive model to study such processes.
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