OpenLB
Open Library of Bioscience
Advanced Search
Science advances
07, 2021;7 (28):

The site of breast cancer metastases dictates their clonal composition and reversible transcriptomic profile.

Jean Berthelet, Verena C Wimmer, Holly J Whitfield, Antonin Serrano, Thomas Boudier, Stefano Mangiola, Michal Merdas, Farrah El-Saafin, David Baloyan, Jordan Wilcox, Steven Wilcox, Adam C Parslow, Anthony T Papenfuss, Belinda Yeo, Matthias Ernst, Bhupinder Pal, Robin L Anderson, Melissa J Davis, Kelly L Rogers, Frédéric Hollande, Delphine Merino
Author Information
  1. Jean Berthelet: Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia. delphine.merino@onjcri.org.au jean.berthelet@onjcri.org.au. ORCID
  2. Verena C Wimmer: Advanced Technology and Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia. ORCID
  3. Holly J Whitfield: Department of Medical Biology, Faculty of Medicine, Dentistry, and Health Science, The University of Melbourne, Parkville, VIC 3010, Australia. ORCID
  4. Antonin Serrano: Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia. ORCID
  5. Thomas Boudier: Advanced Technology and Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia. ORCID
  6. Stefano Mangiola: Department of Medical Biology, Faculty of Medicine, Dentistry, and Health Science, The University of Melbourne, Parkville, VIC 3010, Australia. ORCID
  7. Michal Merdas: Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia. ORCID
  8. Farrah El-Saafin: Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia. ORCID
  9. David Baloyan: Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.
  10. Jordan Wilcox: Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia. ORCID
  11. Steven Wilcox: Advanced Technology and Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  12. Adam C Parslow: Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia. ORCID
  13. Anthony T Papenfuss: Department of Medical Biology, Faculty of Medicine, Dentistry, and Health Science, The University of Melbourne, Parkville, VIC 3010, Australia. ORCID
  14. Belinda Yeo: Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia. ORCID
  15. Matthias Ernst: Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.
  16. Bhupinder Pal: Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.
  17. Robin L Anderson: Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.
  18. Melissa J Davis: Department of Medical Biology, Faculty of Medicine, Dentistry, and Health Science, The University of Melbourne, Parkville, VIC 3010, Australia. ORCID
  19. Kelly L Rogers: Advanced Technology and Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia. ORCID
  20. Frédéric Hollande: Department of Clinical Pathology, Faculty of Medicine, Dentistry, and Health Science, The University of Melbourne, Melbourne, VIC 3000, Australia. ORCID
  21. Delphine Merino: Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia. delphine.merino@onjcri.org.au jean.berthelet@onjcri.org.au. ORCID
PMID: 34233875 DOI: 10.1126/sciadv.abf4408

Abstract

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.

References

  1. Bioinformatics. 2013 Jul 15;29(14):1840-1 [PMID: 23681123]
  2. Cell Rep. 2018 Nov 20;25(8):2208-2222.e7 [PMID: 30463016]
  3. OMICS. 2012 May;16(5):284-7 [PMID: 22455463]
  4. Cell Death Differ. 2020 Oct;27(10):2768-2780 [PMID: 32341449]
  5. Nat Genet. 2020 Jul;52(7):701-708 [PMID: 32424352]
  6. Science. 2014 Jun 20;344(6190):1396-401 [PMID: 24925914]
  7. Nat Protoc. 2012 Apr 05;7(5):839-49 [PMID: 22481527]
  8. Mol Cancer Res. 2010 Oct;8(10):1319-27 [PMID: 20724460]
  9. J Clin Oncol. 2008 Mar 10;26(8):1275-81 [PMID: 18250347]
  10. Med Oncol. 2013 Mar;30(1):388 [PMID: 23292831]
  11. Cancers (Basel). 2019 Oct 16;11(10): [PMID: 31623163]
  12. Nat Commun. 2014 Dec 23;5:5871 [PMID: 25532760]
  13. Mol Ther. 2017 Mar 1;25(3):621-633 [PMID: 28109958]
  14. Cell. 2014 Aug 28;158(5):1110-1122 [PMID: 25171411]
  15. Am J Clin Oncol. 1990 Aug;13(4):294-8 [PMID: 2198793]
  16. Cytokine Growth Factor Rev. 2015 Oct;26(5):489-98 [PMID: 26209885]
  17. Sci Rep. 2019 May 10;9(1):7202 [PMID: 31076648]
  18. Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6140-6145 [PMID: 30850544]
  19. Bioinformatics. 2014 Apr 1;30(7):923-30 [PMID: 24227677]
  20. NPJ Precis Oncol. 2018 Feb 16;2(1):4 [PMID: 29872722]
  21. Nature. 2014 Oct 2;514(7520):54-8 [PMID: 25079331]
  22. JCI Insight. 2018 Aug 23;3(16): [PMID: 30135299]
  23. Cancer Res. 1976 Mar;36(3):889-94 [PMID: 1253177]
  24. Int J Biostat. 2018 Jul 7;14(2): [PMID: 29981281]
  25. Cell. 2007 Nov 16;131(4):669-81 [PMID: 18022362]
  26. Nat Commun. 2018 Nov 29;9(1):5079 [PMID: 30498242]
  27. Cell. 2009 Dec 24;139(7):1315-26 [PMID: 20064377]
  28. Nucleic Acids Res. 2015 Apr 20;43(7):e47 [PMID: 25605792]
  29. Cell. 2018 Jan 11;172(1-2):205-217.e12 [PMID: 29307488]
  30. PLoS One. 2013 Jun 26;8(6):e67316 [PMID: 23840661]
  31. Cancer Cell. 2020 Apr 13;37(4):471-484 [PMID: 32289271]
  32. Cancer Res. 2003 Nov 15;63(22):7785-90 [PMID: 14633704]
  33. Mol Ther. 2008 Apr;16(4):698-706 [PMID: 18362927]
  34. Cell. 2018 May 3;173(4):879-893.e13 [PMID: 29681456]
  35. Genome Res. 2003 Nov;13(11):2498-504 [PMID: 14597658]
  36. Nat Genet. 2013 Jun;45(6):580-5 [PMID: 23715323]
  37. Cancer. 1960 Jan-Feb;13:111-7 [PMID: 14423852]
  38. Genome Res. 2017 May;27(5):849-864 [PMID: 28396521]
  39. Cell Syst. 2015 Dec 23;1(6):417-425 [PMID: 26771021]
  40. Nat Cell Biol. 2020 Mar;22(3):310-320 [PMID: 32144411]
  41. Nat Commun. 2019 Feb 15;10(1):766 [PMID: 30770823]
  42. Nat Rev Clin Oncol. 2018 Feb;15(2):81-94 [PMID: 29115304]
  43. Bioinformatics. 2010 Jan 1;26(1):139-40 [PMID: 19910308]
  44. Nat Methods. 2012 Feb 28;9(3):245-53 [PMID: 22373911]
  45. Commun Biol. 2019 Aug 9;2:306 [PMID: 31428694]
  46. Comput Intell Neurosci. 2016;2016:4037380 [PMID: 27212939]
  47. Cold Spring Harb Symp Quant Biol. 2005;70:149-58 [PMID: 16869748]
  48. Bioinformatics. 2013 Jan 1;29(1):15-21 [PMID: 23104886]
  49. Nature. 2015 Apr 16;520(7547):358-62 [PMID: 25855289]
  50. Nat Commun. 2018 May 23;9(1):2028 [PMID: 29795293]
  51. Oncogene. 2021 Jan;40(1):12-27 [PMID: 33046799]
  52. Front Immunol. 2019 Jul 31;10:1818 [PMID: 31417576]
  53. Nature. 2014 Aug 14;512(7513):155-60 [PMID: 25079324]
  54. J Vis Exp. 2014 Aug 06;(90):e51669 [PMID: 25145579]
  55. Cell. 2019 Jun 13;177(7):1888-1902.e21 [PMID: 31178118]
  56. J Clin Invest. 2018 Apr 2;128(4):1371-1383 [PMID: 29480819]
  57. Nat Med. 2011 Apr;17(4):504-9 [PMID: 21441917]
  58. J Exp Med. 1991 Dec 1;174(6):1483-9 [PMID: 1660525]
  59. J Clin Oncol. 2012 Feb 10;30(5):525-32 [PMID: 22253462]
  60. Cell Metab. 2015 Oct 6;22(4):577-89 [PMID: 26365179]
  61. Nat Rev Cancer. 2015 Aug;15(8):473-83 [PMID: 26156638]
  62. Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):E854-63 [PMID: 26831077]
  63. Curr Med Res Opin. 2015 Mar;31(3):557-74 [PMID: 25651481]
  64. Nat Cell Biol. 2019 Jul;21(7):879-888 [PMID: 31263265]
  65. Nature. 2018 Aug;560(7718):325-330 [PMID: 30089904]
  66. J Clin Invest. 2005 Jan;115(1):44-55 [PMID: 15630443]
  67. Cancer Cell. 2007 Nov;12(5):445-56 [PMID: 17996648]
  68. Nature. 2013 Sep 19;501(7467):365-72 [PMID: 24048069]
  69. Nat Rev Cancer. 2012 Apr 19;12(5):323-34 [PMID: 22513401]
  70. Signal Transduct Target Ther. 2017;2: [PMID: 29158945]

MeSH Term

Breast Neoplasms
Female
Humans
Liver Neoplasms
Lung Neoplasms
Neoplasm Metastasis
Transcriptome
Tumor Microenvironment
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 53

Word Cloud

Created with Highcharts 10.0.0metastaseslivercancerclonalheterogeneitybreastsubclonescompositionlungsfoundreversiblesignaturelungtumorpathwayIntratumoraldriverprogressionnatureinteractivenetworkinvolvedprocessremainsunclearoptimizeduseopticalbarcodingvisualizecharacterize31vivomappingthousandstwoclinicallyrelevantsiteshighlypolyclonalFurthermoretranscriptomevariedaccordingmetastaticnichealsoidentifiedniche-drivenconservedcollectedpatientautopsiesAmongnecrosisfactor-αup-regulatedcomparedinhibitionaffectedmetastasisdiversityresultshighlightcellularmolecularobservedlargelydictatedmicroenvironmentsitedictatestranscriptomicprofile

Similar Articles

Cited By