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

Research output: Contribution to journalArticle

190 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)827-838
Number of pages12
JournalCell Stem Cell
Volume18
Issue number6
DOIs
Publication statusPublished - 2016 Jun 2

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Fingerprint Dive into the research topics of 'A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis'. Together they form a unique fingerprint.

  • Cite this

    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. (2016). A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis. Cell Stem Cell, 18(6), 827-838. https://doi.org/10.1016/j.stem.2016.04.003