Phenotypic heterogeneity of 2D organoid reflects clinical tumor characteristics

Shiki Fujino, Aya Ito, Masayuki Ohue, Masayoshi Yasui, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori, Norikatsu Miyoshi

Research output: Contribution to journalArticle

Abstract

Unlike cancer cell lines, tumors and primary cultured cells exhibit phenotypic heterogeneity. Although methods for establishing organoids within three-dimensional (3D) gels are well-known, the growth is slower than that of two-dimensional (2D) cultured cells and many niche factors need to be added. In this study, we established primary cultured organoid in 2D culture (2D organoid; 2DO) in a reproducible manner and with clinical phenotypic heterogeneity. The 2DO contained cancer stem cells (CSCs) expressing CD44 and CD133. The addition of basic fibroblast growth factor and transforming growth factor-β as niche factors was necessary to establish the 2DO and maintain the CSC population. The established 2DO showed sufficient proliferation, and the culture could be transferred to the 3D culture. Morphological analysis of the xenograft induced by 2DO reflected parental tumor differentiation, and gene expression in the 2DO was similar to that in the parental tumor. In vitro drug sensitivity analysis using the 2DO reflected individual clinical courses. The 2DO is an in vitro personal cancer model, and the results of the drug sensitivity assessment may be useful for introducing clinical chemotherapy agents in personalized medicine.

Original languageEnglish
Pages (from-to)332-339
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume513
Issue number2
DOIs
Publication statusPublished - May 28 2019
Externally publishedYes

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Organoids
Tumors
Cells
Stem cells
Neoplastic Stem Cells
Neoplasms
Chemotherapy
Transforming Growth Factors
Fibroblast Growth Factor 2
Cultured Tumor Cells
Heterografts
Gene expression
Pharmaceutical Preparations
Precision Medicine
Sensitivity analysis
Medicine
Gels
Cultured Cells
Gene Expression
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Phenotypic heterogeneity of 2D organoid reflects clinical tumor characteristics. / Fujino, Shiki; Ito, Aya; Ohue, Masayuki; Yasui, Masayoshi; Mizushima, Tsunekazu; Doki, Yuichiro; Mori, Masaki; Miyoshi, Norikatsu.

In: Biochemical and Biophysical Research Communications, Vol. 513, No. 2, 28.05.2019, p. 332-339.

Research output: Contribution to journalArticle

Fujino, Shiki ; Ito, Aya ; Ohue, Masayuki ; Yasui, Masayoshi ; Mizushima, Tsunekazu ; Doki, Yuichiro ; Mori, Masaki ; Miyoshi, Norikatsu. / Phenotypic heterogeneity of 2D organoid reflects clinical tumor characteristics. In: Biochemical and Biophysical Research Communications. 2019 ; Vol. 513, No. 2. pp. 332-339.
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