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

Masayuki Fujii, Mariko Shimokawa, Shoichi Date, Ai Takano, Mami Matano, Kosaku Nanki, Yuki Ohta, Kohta Toshimitsu, Yoshihiro Nakazato, Kenta Kawasaki, Toshio Uraoka, Toshiaki Watanabe, Takanori Kanai, Toshiro Sato

研究成果: Article査読

339 被引用数 (Scopus)

抄録

Summary 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.

本文言語English
ページ(範囲)827-838
ページ数12
ジャーナルCell stem cell
18
6
DOI
出版ステータスPublished - 2016 6 2

ASJC Scopus subject areas

  • 分子医療
  • 遺伝学
  • 細胞生物学

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