A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis
Open accessAbstract
Colorectal tumor is a heterogeneous disease, with varying clinical presentation and prognosis in patients. To establish a platform encompassing this diversity, we generated 55 colorectal tumor organoid lines from a range of histological subtypes and clinical stages, including rare subtypes. Each line was defined by gene expression signatures and optimized for organoid culture according to niche factor requirements. In vitro and in xenografts, the organoids reproduced the histopathological grade and differentiation capacity of their parental tumors. Notably, we found that niche-independent growth is predominantly associated with the adenoma-carcinoma transition reflecting accumulation of multiple mutations. For matched pairs of primary and metastatic organoids, which had similar genetic profiles and niche factor requirements, the metastasis-derived organoids exhibited higher metastatic capacity. These observations underscore the importance of genotype-phenotype analyses at a single-patient level and the value of our resource to provide insights into colorectal tumorigenesis and patient-centered therapeutic development.
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For some tumors, tumor-forming cells can be enriched by sorting before culture.
“While for some tumors it may be possible to enrich for tumor-forming cells by sorting a priori58”
From Organoids (2022) · cites this paper as [58]
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- Authors
- Fujii, M., Shimokawa, M., Date, S., Takano, A., Matano, M., Nanki, K., Ohta, Y., Toshimitsu, K., Nakazato, Y., Kawasaki, K., Uraoka, T., Watanabe, T., Kanai, T., & Sato, T.
- Affiliations
- Keio University (JP)
- Otsuka (Japan) (JP)
- The University of Tokyo (JP)
- Corresponding author
- Sato, Toshiro
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 18
- Issue
- 6
- Pages
- 827-838
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2403475582
- Cited by
- 852
- References
- 38
- Citations by year
- 2026: 63 · 2025: 86 · 2024: 84 · 2023: 102 · 2022: 116 · 2021: 114 · 2020: 98 · 2019: 67 · 2018: 62 · 2017: 39 · 2016: 12 · 2015: 1 · 2013: 1 · 2012: 2
- FWCI
- 32.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Agency for Medical Research and Development
- Research Center Network for Realization of Regenerative Medicine
- Ministry of Education, Culture, Sports, Science and Technology (2611507)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- colorectal cancer, tumor organoids, niche factors, carcinogenesis, adenoma-carcinoma sequence, metastasis, histological subtypes, gene expression signatures, genotype-phenotype correlation, xenografts
- MeSH terms
- Animals, Epidermal Growth Factor, Humans, Male, Mutation, Organoids, Transplantation, Heterologous, Tumor Cells, Cultured, Colorectal Neoplasms, Genome, Human, Gene Expression Regulation, Neoplastic, Transforming Growth Factor beta, Mice, SCID, Mice, Inbred NOD, Genetic Heterogeneity, Gene Expression Profiling, Wnt Proteins, Stem Cell Niche, Carcinogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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