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Cell Stem Cell. 2016 Jun 2;18(6):827-38. doi: 10.1016/j.stem.2016.04.003. Epub 2016 May 19.

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

Author information

1
Department of Gastroenterology, Cancer Center, Keio University School of Medicine, Tokyo 160-8582, Japan; Department of Surgical Oncology, The University of Tokyo, Tokyo 113-8654, Japan.
2
Department of Gastroenterology, Cancer Center, Keio University School of Medicine, Tokyo 160-8582, Japan.
3
Department of Gastroenterology, Cancer Center, Keio University School of Medicine, Tokyo 160-8582, Japan; Fujii Memorial Research Institute, Otsuka Pharmaceutical Company, Limited, Shiga 520-0106, Japan.
4
Division for Research and Development of Minor Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo 160-8582, Japan.
5
Department of Surgical Oncology, The University of Tokyo, Tokyo 113-8654, Japan.
6
Department of Gastroenterology, Cancer Center, Keio University School of Medicine, Tokyo 160-8582, Japan. Electronic address: t.sato@keio.jp.

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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PMID:
27212702
DOI:
10.1016/j.stem.2016.04.003
[Indexed for MEDLINE]
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