Distinct types of tumor-initiating cells form human colon cancer tumors and metastases
Open accessAbstract
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.
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TICs that have the capacity to self-renew and maintain long-term tumor growth are usually rare within the tumor mass but highly enriched within spheroid cultures.
“Moreover, TICs that have the capacity to self-renew and maintain long-term tumor growth are usually rare within the tumor mass but highly enriched within spheroid cultures (Dieter et al., 2011;Ishiguro et al., 2017).”
From Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer (2021) · cites this paper as Dieter et al., 2011
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- Authors
- Dieter, S. M., Ball, C. R., Hoffmann, C. M., Nowrouzi, A., Herbst, F., Zavidij, O., Abel, U., Arens, A., Weichert, W., Brand, K., Koch, M., Weitz, J., Schmidt, M., von Kalle, C., & Glimm, H.
- Affiliations
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- Corresponding author
- Glimm, Hanno
- ORCID
- Venue
- Cell stem cell
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 9
- Issue
- 4
- Pages
- 357-365
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2043772256
- Cited by
- 297
- References
- 36
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 18 · 2022: 13 · 2021: 18 · 2020: 17 · 2019: 35 · 2018: 20 · 2017: 21 · 2016: 22 · 2015: 31 · 2014: 22 · 2013: 30 · 2012: 31
- FWCI
- 13.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Keywords
- colon cancer, cancer stem cells, cellular heterogeneity, self-renewal, metastasis, transit amplifying cells, bone marrow, xenotransplantation, cancer therapy targets
- MeSH terms
- Aged, Animals, Bone Marrow, Colonic Neoplasms, Female, Humans, Male, Middle Aged, Neoplasm Metastasis, Time Factors, Tumor Cells, Cultured, Neoplastic Stem Cells, Mice, SCID, Spheroids, Cellular, Cell Proliferation, Mice
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