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The site of breast cancer metastases dictates their clonal composition and reversible transcriptomic profile.
Berthelet, Jean; Wimmer, Verena C; Whitfield, Holly J; Serrano, Antonin; Boudier, Thomas; Mangiola, Stefano; Merdas, Michal; El-Saafin, Farrah; Baloyan, David; Wilcox, Jordan; Wilcox, Steven; Parslow, Adam C; Papenfuss, Anthony T; Yeo, Belinda; Ernst, Matthias; Pal, Bhupinder; Anderson, Robin L; Davis, Melissa J; Rogers, Kelly L; Hollande, Frédéric; Merino, Delphine.
Afiliación
  • Berthelet J; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia. delphine.merino@onjcri.org.au jean.berthelet@onjcri.org.au.
  • Wimmer VC; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia.
  • Whitfield HJ; Advanced Technology and Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Serrano A; Department of Medical Biology, Faculty of Medicine, Dentistry, and Health Science, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Boudier T; Department of Medical Biology, Faculty of Medicine, Dentistry, and Health Science, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Mangiola S; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Merdas M; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.
  • El-Saafin F; Department of Medical Biology, Faculty of Medicine, Dentistry, and Health Science, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Baloyan D; Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Wilcox J; Advanced Technology and Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Wilcox S; Department of Medical Biology, Faculty of Medicine, Dentistry, and Health Science, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Parslow AC; Department of Medical Biology, Faculty of Medicine, Dentistry, and Health Science, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Papenfuss AT; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Yeo B; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.
  • Ernst M; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia.
  • Pal B; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.
  • Anderson RL; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia.
  • Davis MJ; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.
  • Rogers KL; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia.
  • Hollande F; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.
  • Merino D; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia.
Sci Adv ; 7(28)2021 07.
Article en En | MEDLINE | ID: mdl-34233875
Intratumoral heterogeneity is a driver of breast cancer progression, but the nature of the clonal interactive network involved in this process remains unclear. Here, we optimized the use of optical barcoding to visualize and characterize 31 cancer subclones in vivo. By mapping the clonal composition of thousands of metastases in two clinically relevant sites, the lungs and liver, we found that metastases were highly polyclonal in lungs but not in the liver. Furthermore, the transcriptome of the subclones varied according to their metastatic niche. We also identified a reversible niche-driven signature that was conserved in lung and liver metastases collected during patient autopsies. Among this signature, we found that the tumor necrosis factor-α pathway was up-regulated in lung compared to liver metastases, and inhibition of this pathway affected metastasis diversity. These results highlight that the cellular and molecular heterogeneity observed in metastases is largely dictated by the tumor microenvironment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Neoplasias Hepáticas / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Sci Adv Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Neoplasias Hepáticas / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Sci Adv Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos