Abstract PO-031: MetMap: A map of metastatic potential of human cancer cell lines

Most deaths from cancer are explained by metastasis, and yet large-scale metastasis research has been impractical due to the complexity of in vivo models. Here, we introduce an in vivo barcoding strategy capable of determining the metastatic potential of human cancer cell lines in murine xenografts at scale. We validated the robustness, scalability and reproducibility of the method, and applied it to 500 cell lines spanning 21 solid cancer types. We created a first-generation Metastasis Map (MetMap) that reveals organ-specific patterns of metastasis and allows relating those patterns to clinical and genomic features. We demonstrated the utility of MetMap by exploring the molecular basis of breast cancers capable of metastasizing to the brain – a principal cause of death in these patients. We found that breast cancers capable of metastasizing to the brain had unexpected evidence of altered lipid metabolism. Perturbing lipid metabolism curbed brain metastasis development, suggesting a therapeutic strategy to combat the disease and demonstrating the utility of MetMap as a public resource to support metastasis research. Citation Format: 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. Vander Heiden, Todd R. Golub. MetMap: A map of metastatic potential of human cancer cell lines [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-031.