Nutrient requirements of organ-specific metastasis in breast cancer
Affiliations
- 1 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
- 2 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
- 3 Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- 4 Steele Laboratories of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
- 5 Department of Genetics, Harvard Medical School, Boston, MA, USA.
- 6 Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
- 7 Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
- 8 Institute of Chemical Technologies and Analytics, Technische Universität Wien, Vienna, Austria.
- 9 Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.
- 10 Faculty of Medicine, Heidelberg University, Heidelberg, Germany.
- 11 Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland.
- 12 Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
- 13 Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
- 14 Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, China.
- 15 Department of Genetics, Harvard Medical School, Boston, MA, USA. [email protected].
- 16 Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. [email protected].
- 17 Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA. [email protected].
- 18 Blavatnik Institute, Harvard Medical School, Boston, MA, USA. [email protected].
- 19 Steele Laboratories of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [email protected].
- 20 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. [email protected].
- 21 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. [email protected].
- 22 Broad Institute of MIT and Harvard, Cambridge, MA, USA. [email protected].
- 23 Dana-Farber Cancer Institute, Boston, MA, USA. [email protected].
- PMID: 41501456
- PMCID: PMC12851942
- DOI: 10.1038/s41586-025-09898-9
Abstract
Cancer metastasis is a major contributor to patient morbidity and mortality1, yet the factors that determine the organs where cancers can metastasize are incompletely understood. Here we quantify the absolute levels of 124 metabolites in multiple tissues in mice and investigate how this relates to the ability of breast cancer cells to grow in different organs. We engineered breast cancer cells with broad metastatic potential to be auxotrophic for specific nutrients and assessed their ability to colonize different tissue sites. We then asked how tumour growth in different tissues relates to nutrient availability and tumour biosynthetic activity. We find that single nutrients alone do not define the sites where breast cancer cells can grow as metastases. In addition, we identify purine synthesis as a requirement for tumour growth and metastasis across many tissues and find that this phenotype is independent of tissue nucleotide availability or tumour de novo nucleotide synthesis activity. These data suggest that a complex interplay between multiple nutrients within the microenvironment dictates potential sites of metastatic cancer growth, and highlights the interdependence between extrinsic environmental factors and intrinsic cellular properties in influencing where breast cancer cells can grow as metastases.