Nature 2020 Dec;588(7837):331-336. doi: 10.1038/s41586-020-2969-2. Epub 2020 Dec 9.
A metastasis map of human cancer cell lines
Xin Jin 1, Zelalem Demere 2, Karthik Nair 2, Ahmed Ali 2 3, Gino B Ferraro 4, Ted Natoli 2, Amy Deik 2, Lia Petronio 2, Andrew A Tang 2, Cong Zhu 2, Li Wang 2, Danny Rosenberg 2, Vamsi Mangena 5, Jennifer Roth 2, Kwanghun Chung 2 5, Rakesh K Jain 4 6, Clary B Clish 2, Matthew G Vander Heiden 2 3 7, Todd R Golub 8 9 10Affiliations expand
- PMID: 33299191
- PMCID: PMC8439149
- DOI: 10.1038/s41586-020-2969-2
Free PMC article
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.
Comment in
- Heterogeneity in Metastatic Potential of Cancer Cells Is Revealed En Masse.Viswanath P, Welm AL.Cancer Cell. 2021 Feb 8;39(2):148-150. doi: 10.1016/j.ccell.2021.01.017.PMID: 33561396
Similar articles
- Genes that mediate breast cancer metastasis to the brain.Bos PD, Zhang XH, Nadal C, Shu W, Gomis RR, Nguyen DX, Minn AJ, van de Vijver MJ, Gerald WL, Foekens JA, Massagué J.Nature. 2009 Jun 18;459(7249):1005-9. doi: 10.1038/nature08021. Epub 2009 May 6.PMID: 19421193 Free PMC article.
- Expression of Lipid Metabolism-Related Proteins in Metastatic Breast Cancer.Jung YY, Kim HM, Koo JS.PLoS One. 2015 Sep 3;10(9):e0137204. doi: 10.1371/journal.pone.0137204. eCollection 2015.PMID: 26334757 Free PMC article.
- Role of KCNMA1 gene in breast cancer invasion and metastasis to brain.Khaitan D, Sankpal UT, Weksler B, Meister EA, Romero IA, Couraud PO, Ningaraj NS.BMC Cancer. 2009 Jul 29;9:258. doi: 10.1186/1471-2407-9-258.PMID: 19640305 Free PMC article.
- Preclinical recapitulation of antiangiogenic drug clinical efficacies using models of early or late stage breast cancer metastatis.Kerbel RS, Guerin E, Francia G, Xu P, Lee CR, Ebos JM, Man S.Breast. 2013 Aug;22 Suppl 2:S57-65. doi: 10.1016/j.breast.2013.07.011.PMID: 24074794 Review.
- [Brain metastasis of breast tumors and blood brain barrier].Diéras V, Pierga JY.Bull Cancer. 2011 Apr;98(4):385-9. doi: 10.1684/bdc.2011.1336.PMID: 21527366 Review. French.
Cited by 32 articles
- Fatty acid synthase (FASN) regulates the mitochondrial priming of cancer cells.Schroeder B, Vander Steen T, Espinoza I, Venkatapoorna CMK, Hu Z, Silva FM, Regan K, Cuyàs E, Meng XW, Verdura S, Arbusà A, Schneider PA, Flatten KS, Kemble G, Montero J, Kaufmann SH, Menendez JA, Lupu R.Cell Death Dis. 2021 Oct 21;12(11):977. doi: 10.1038/s41419-021-04262-x.PMID: 34675185 Free PMC article.
- Identification of antiviral phytochemicals as a potential SARS-CoV-2 main protease (Mpro) inhibitor using docking and molecular dynamics simulations.Patel CN, Jani SP, Jaiswal DG, Kumar SP, Mangukia N, Parmar RM, Rawal RM, Pandya HA.Sci Rep. 2021 Oct 13;11(1):20295. doi: 10.1038/s41598-021-99165-4.PMID: 34645849 Free PMC article.
- Identification of nuclear export inhibitor-based combination therapies in preclinical models of triple-negative breast cancer.Rashid NS, Hairr NS, Murray G, Olex AL, Leftwich TJ, Grible JM, Reed J, Dozmorov MG, Harrell JC.Transl Oncol. 2021 Dec;14(12):101235. doi: 10.1016/j.tranon.2021.101235. Epub 2021 Oct 7.PMID: 34628286 Free PMC article.
- Fatty acid oxidation is a druggable gateway regulating cellular plasticity for driving metastasis in breast cancer.Loo SY, Toh LP, Xie WH, Pathak E, Tan W, Ma S, Lee MY, Shatishwaran S, Yeo JZZ, Yuan J, Ho YY, Peh EKL, Muniandy M, Torta F, Chan J, Tan TJ, Sim Y, Tan V, Tan B, Madhukumar P, Yong WS, Ong KW, Wong CY, Tan PH, Yap YS, Deng LW, Dent R, Foo R, Wenk MR, Lee SC, Ho YS, Lim EH, Tam WL.Sci Adv. 2021 Oct 8;7(41):eabh2443. doi: 10.1126/sciadv.abh2443. Epub 2021 Oct 6.PMID: 34613780 Free PMC article.
- ARMT: An automatic RNA-seq data mining tool based on comprehensive and integrative analysis in cancer research.Huang G, Zhang H, Qu Y, Huang K, Gong X, Wei J, Du H.Comput Struct Biotechnol J. 2021 Aug 10;19:4426-4434. doi: 10.1016/j.csbj.2021.08.009. eCollection 2021.PMID: 34471489 Free PMC article.
References
- Barretina J. et al.The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483, 603–7 (2012). – PMC – PubMed
Editor do blog: Julio Pereira – Neurocirugião – São Paulo CRM/SP 163.113 Site para Consulta: https://www.julio-pereira.com/ Consultório: (11)99503-8838 (WhatsApp) / (11)4200-2300 Atuando no Hospital Sírio-Libanês e na BP – A Beneficência Portuguesa de São Paulo.
