Succession of transiently active tumor-initiating cell clones in human pancreatic cancer xenografts
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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.
Details
Original language | English |
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Pages (from-to) | 918-932 |
Number of pages | 15 |
Journal | EMBO molecular medicine |
Volume | 9 |
Issue number | 7 |
Publication status | Published - Jul 2017 |
Peer-reviewed | Yes |
External IDs
PubMed | 28526679 |
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Keywords
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- clonal dynamics, pancreatic cancer, phenotypic plasticity, tumor-initiating cells