A metastasis map of human cancer cell lines

Xin Jin (), Zelalem Demere, Karthik Nair, Ahmed Ali, Gino B. Ferraro, Ted Natoli, Amy Deik, Lia Petronio, Andrew A. Tang, Cong Zhu, Li Wang, Danny Rosenberg, Vamsi Mangena, Jennifer Roth, Kwanghun Chung, Rakesh K. Jain, Clary B. Clish, Matthew G. Heiden and Todd R. Golub ()
Additional contact information
Xin Jin: Broad Institute of MIT and Harvard
Zelalem Demere: Broad Institute of MIT and Harvard
Karthik Nair: Broad Institute of MIT and Harvard
Ahmed Ali: Broad Institute of MIT and Harvard
Gino B. Ferraro: Massachusetts General Hospital
Ted Natoli: Broad Institute of MIT and Harvard
Amy Deik: Broad Institute of MIT and Harvard
Lia Petronio: Broad Institute of MIT and Harvard
Andrew A. Tang: Broad Institute of MIT and Harvard
Cong Zhu: Broad Institute of MIT and Harvard
Li Wang: Broad Institute of MIT and Harvard
Danny Rosenberg: Broad Institute of MIT and Harvard
Vamsi Mangena: Massachusetts Institute of Technology
Jennifer Roth: Broad Institute of MIT and Harvard
Kwanghun Chung: Broad Institute of MIT and Harvard
Rakesh K. Jain: Massachusetts General Hospital
Clary B. Clish: Broad Institute of MIT and Harvard
Matthew G. Heiden: Broad Institute of MIT and Harvard
Todd R. Golub: Broad Institute of MIT and Harvard

Nature, 2020, vol. 588, issue 7837, 331-336

Abstract: Abstract Most deaths from cancer are explained by metastasis, and yet large-scale metastasis research has been impractical owing to the complexity of in vivo models. Here we introduce an in vivo barcoding strategy that is capable of determining the metastatic potential of human cancer cell lines in mouse xenografts at scale. We validated the robustness, scalability and reproducibility of the method and applied it to 500 cell lines1,2 spanning 21 types of solid tumour. We created a first-generation metastasis map (MetMap) that reveals organ-specific patterns of metastasis, enabling these patterns to be associated with clinical and genomic features. We demonstrate the utility of MetMap by investigating the molecular basis of breast cancers capable of metastasizing to the brain—a principal cause of death in patients with this type of cancer. Breast cancers capable of metastasizing to the brain showed evidence of altered lipid metabolism. Perturbation of lipid metabolism in these cells curbed brain metastasis development, suggesting a therapeutic strategy to combat the disease and demonstrating the utility of MetMap as a resource to support metastasis research.

Date: 2020
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DOI: 10.1038/s41586-020-2969-2

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