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Distinct types of tumor-initiating cells form human colon cancer tumors and metastases

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Human colon cancer harbors a small subfraction of tumor-initiating cells (TICs) that is assumed to be a functionally homogeneous stem-cell-like population driving tumor maintenance and metastasis formation. We found unexpected cellular heterogeneity within the TIC compartment, which contains three t...

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Main Authors: Dieter, Sebastian M. (Author) , Ball, Claudia R. (Author) , Hoffmann, Christopher M. (Author) , Nowrouzi, Ali (Author) , Herbst, Friederike (Author) , Zavidij, Oksana (Author) , Abel, Ulrich (Author) , Arens, Anne (Author) , Weichert, Wilko (Author) , Brand, Karsten (Author) , Koch, Moritz (Author) , Weitz, Jürgen (Author) , Schmidt, Manfred (Author) , Kalle, Christof von (Author) , Glimm, Hanno (Author)
Format: Article (Journal)
Language:English
Published: October 7, 2011
In: Cell stem cell
Year: 2011, Volume: 9, Issue: 4, Pages: 357-365
ISSN:1875-9777
DOI:10.1016/j.stem.2011.08.010
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.stem.2011.08.010
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1934590911003912
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Author Notes:Sebastian M. Dieter, Claudia R. Ball, Christopher M. Hoffmann, Ali Nowrouzi, Friederike Herbst, Oksana Zavidij, Ulrich Abel, Anne Arens, Wilko Weichert, Karsten Brand, Moritz Koch, Jürgen Weitz, Manfred Schmidt, Christof von Kalle, and Hanno Glimm
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Summary:Human colon cancer harbors a small subfraction of tumor-initiating cells (TICs) that is assumed to be a functionally homogeneous stem-cell-like population driving tumor maintenance and metastasis formation. We found unexpected cellular heterogeneity within the TIC compartment, which contains three types of TICs. Extensively self-renewing long-term TICs (LT-TICs) maintained tumor formation in serial xenotransplants. Tumor transient amplifying cells (T-TACs) with limited or no self-renewal capacity contributed to tumor formation only in primary mice. Rare delayed contributing TICs (DC-TICs) were exclusively active in secondary or tertiary mice. Bone marrow was identified as an important reservoir of LT-TICs. Metastasis formation was almost exclusively driven by self-renewing LT-TICs. Our results demonstrate that tumor initiation, self-renewal, and metastasis formation are limited to particular subpopulations of TICs in primary human colon cancer. We identify LT-TICs as a quantifiable target for therapies aimed toward eradication of self-renewing tumorigenic and metastatic colon cancer cells.
Item Description:Gesehen am 10.06.2022
Physical Description:Online Resource
ISSN:1875-9777
DOI:10.1016/j.stem.2011.08.010

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