13C and15N natural isotope abundance reflects breast cancer cell metabolism.
Breast cancer is the most common cancer in women worldwide. Despite the information provided by anatomopathological assessment and molecular markers (such as receptor expression ER, PR, HER2), breast cancer therapies and prognostics depend on the metabolic properties of tumor cells. However, metabolomics have not provided a robust and congruent biomarker yet, likely because individual metabolite contents are insufficient to encapsulate all of the alterations in metabolic fluxes. Here, we took advantage of natural13C and15N isotope abundance to show there are isotopic differences between healthy and cancer biopsy tissues or between healthy and malignant cultured cell lines. Isotope mass balance further suggests that these differences are mostly related to lipid metabolism, anaplerosis and urea cycle, three pathways known to be impacted in malignant cells. Our results demonstrate that the isotope signature is a good descriptor of metabolism since it integrates modifications in C partitioning and N excretion altogether. Our present study is thus a starting point to possible clinical applications such as patient screening and biopsy characterization in every cancer that is associated with metabolic changes.
EBSI team, CEISAM, University of Nantes-CNRS UMR 6230, 2 rue de la Houssinière BP 92208, F-44322 Nantes, France.|Cancer Metabolism and Genetics Group, The John Curtin School of Medical Research, The Australian National University, Canberra 2601 ACT, Australia.
Illa
I
Tea
EBSI team, CEISAM, University of Nantes-CNRS UMR 6230, 2 rue de la Houssinière BP 92208, F-44322 Nantes, France.|Spectromaitrise, CAPACITÉS SAS, 26 Bd Vincent Gâche, 44200 Nantes, France.
Estelle
E
Martineau
EBSI team, CEISAM, University of Nantes-CNRS UMR 6230, 2 rue de la Houssinière BP 92208, F-44322 Nantes, France.
Ingrid
I
Antheaume
EBSI team, CEISAM, University of Nantes-CNRS UMR 6230, 2 rue de la Houssinière BP 92208, F-44322 Nantes, France.
Julie
J
Lalande
Plateforme Métabolisme-Métabolome, Bâtiment 630 IPS2, Université Paris-Sud, 91405 Orsay cedex, France.
Caroline
C
Mauve
Plateforme Métabolisme-Métabolome, Bâtiment 630 IPS2, Université Paris-Sud, 91405 Orsay cedex, France.
Francoise
F
Gilard
CRCNA, UMR INSERM U892/CNRS 6299/Université de Nantes, Team 8 «Cell survival and tumor escape in breast cancers», Institut de Recherche en Santé de l'Université de Nantes, 8 quai Moncousu, BP 70721, 44 007 Nantes cedex 1, France.
Sophie
S
Barillé-Nion
Cancer Metabolism and Genetics Group, The John Curtin School of Medical Research, The Australian National University, Canberra 2601 ACT, Australia.
Anneke C
AC
Blackburn
Research School of Biology, The Australian National University, Canberra 2601 ACT, Australia.
Guillaume
G
Tcherkez
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