Succession of transiently active tumor-initiating cell clones in human pancreatic cancer xenografts

EMBO Molecular Medicine
Claudia R BallHanno Glimm

Abstract

Although tumor-initiating cell (TIC) self-renewal has been postulated to be essential in progression and metastasis formation of human pancreatic adenocarcinoma (PDAC), clonal dynamics of TICs within PDAC tumors are yet unknown. Here, we show that long-term progression of PDAC in serial xenotransplantation is driven by a succession of transiently active TICs producing tumor cells in temporally restricted bursts. Clonal tracking of individual, genetically marked TICs revealed that individual tumors are generated by distinct sets of TICs with very little overlap between subsequent xenograft generations. An unexpected functional and phenotypic plasticity of pancreatic TICs in vivo underlies the recruitment of inactive TIC clones in serial xenografts. The observed clonal succession of TIC activity in serial xenotransplantation is in stark contrast to the continuous activity of limited numbers of self-renewing TICs within a fixed cellular hierarchy observed in other epithelial cancers and emphasizes the need to target TIC activation, rather than a fixed TIC population, in PDAC.

References

Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·C C FraserR K Humphries
Jan 1, 1992·Current Topics in Microbiology and Immunology·I R Lemischka
Feb 13, 1992·The New England Journal of Medicine·A L Warshaw, C Fernández-del Castillo
Feb 1, 1990·Genes & Development·C T Jordan, I R Lemischka
Oct 10, 1998·Journal of Virology·T DullL Naldini
Jul 19, 2001·Annals of the New York Academy of Sciences·M SchmidtC Von Kalle
Nov 2, 2001·Nature·T ReyaI L Weissman
Jan 17, 2003·The New England Journal of Medicine·Salima Hacein-Bey-AbinaAlain Fischer
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Muhammad Al-HajjMichael F Clarke
Nov 24, 2006·Nature·Lucia Ricci-VitianiRuggero De Maria
Feb 7, 2007·Cancer Research·Chenwei LiDiane M Simeone
Jun 6, 2007·Proceedings of the National Academy of Sciences of the United States of America·Piero DalerbaMichael F Clarke
Jul 21, 2007·Science·Priscilla N KellyAndreas Strasser
Dec 1, 2007·Nature Methods·Manfred SchmidtChristof von Kalle
Jun 3, 2008·Gastroenterology·Volker FendrichAnirban Maitra
Dec 5, 2008·Nature·Elsa QuintanaSean J Morrison
Dec 10, 2008·Blood·John E Dick
Apr 11, 2009·Nature·Michael R StrattonP Andrew Futreal
Nov 7, 2009·Science·Luigi Naldini
Dec 8, 2009·Nature Medicine·Richard GabrielManfred Schmidt
Jan 15, 2010·The Journal of Clinical Investigation·John P MorrisMatthias Hebrok
Feb 2, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·J FerlayE Steliarova-Foucher
Apr 30, 2010·The New England Journal of Medicine·Manuel Hidalgo
Jul 9, 2010·CA: a Cancer Journal for Clinicians·Ahmedin JemalElizabeth Ward
Jul 31, 2010·Nature Protocols·Anna ParuzynskiChristof von Kalle
Sep 18, 2010·Nature Reviews. Genetics·Matthew MeyersonGad Getz
Oct 29, 2010·Nature·Peter J CampbellP Andrew Futreal
Oct 29, 2010·Nature·Shinichi YachidaChristine A Iacobuzio-Donahue
Nov 12, 2010·The New England Journal of Medicine·Kaan BoztugChristoph Klein
Mar 15, 2011·Nature·Nicholas NavinMichael Wigler
May 13, 2011·The New England Journal of Medicine·Thierry ConroyUNKNOWN PRODIGE Intergroup
Aug 9, 2011·Nature Biotechnology·Richard GabrielChristof von Kalle
Sep 29, 2011·Gastroenterology·Chenwei LiDiane M Simeone
Oct 11, 2011·Cell Stem Cell·Sebastian M DieterHanno Glimm
Oct 18, 2011·BMC Genomics·M Aleksi KallioEija I Korpelainen
Jan 13, 2012·Nature Reviews. Cancer·Long V NguyenConnie J Eaves
Mar 24, 2012·Cancer Cell·Jeffrey A MageeSean J Morrison

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Citations

Feb 13, 2019·Cells·Karl Roland EhrenbergClaudia R Ball
Oct 7, 2017·Nature Medicine·Eduard Batlle, Hans Clevers
Aug 11, 2019·Cancers·Eva Rodriguez-AznarPatrick C Hermann
Sep 29, 2019·Journal of Clinical Medicine·Mohit Kumar Jolly, Toni Celià-Terrassa
Nov 30, 2018·Nature Cell Biology·Devon A LawsonZena Werb
May 22, 2019·Journal of Clinical Medicine·Kelvin K TsaiYuval Shaked
May 29, 2018·Cancer Discovery·Christoph HeiningHanno Glimm
May 6, 2021·International Journal of Molecular Sciences·Susmita BarmanPunita Dhawan
Jun 18, 2021·Frontiers in Oncology·Shenq-Shyang HuangKelvin K Tsai
Jul 3, 2021·Cancers·Sophie C LodestijnMaarten F Bijlsma

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Datasets Mentioned

BETA
EGAS00001000882
GSE59118

Methods Mentioned

BETA
xenografts
xenograft
transgenic
exome
chip
flow cytometry
transfection
454
Assay
PCR

Software Mentioned

samtools mpileup
FACSDIVA
BWA aln
Chipster
ELDA
VarScan2
samtools merge
bcftools

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