Cited by 852Cancer Cells and MetastasisColorectal Cancer Treatments and StudiesGenetic factors in colorectal cancer

A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis

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Fujii, Masayuki, Shimokawa, Mariko, Date, Shoichi, Takano, Ai, Matano, Mami, Nanki, Kosaku, Ohta, Yuki, Toshimitsu, Kohta +6 more·2016·Cell Stem Cell

Abstract

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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Crossref · 10.1016/j.stem.2016.04.003

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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
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
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

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