Modeling tumor development and metastasis using paired organoids derived from patients with colorectal cancer liver metastases

He Li, Weixing Dai, Xi Xia, Renjie Wang, Jing Zhao, Lingyu Han, Shaobo Mo, Wenqiang Xiang, Lin Du, Guangya Zhu, Jingjing Xie, Jun Yu, Nan Liu, Mingzhu Huang, Jidong Zhu, Guoxiang Cai

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor metastasis accounts for the majority of cancer-related deaths; it is therefore important to develop preclinical models that faithfully recapitulate disease progression. Here, we generated paired organoids derived from primary tumors and matched liver metastases in the same colorectal cancer (CRC) patients. Despite the fact that paired organoids exhibit comparable gene expression and cell morphology, organoids from metastatic lesions demonstrate more aggressive phenotypes, tumorigenesis, and metastatic capacity than those from primary lesions. Transcriptional analyses of the paired organoids reveal signature genes and pathways altered during the progression of CRC, including SOX2. Further study shows that inducible knockdown of SOX2 attenuated invasion, proliferation, and liver metastasis outgrowth. Taken together, we use patient-derived paired primary and metastatic cancer organoids to model CRC metastasis and illustrate that SOX2 is associated with CRC progression and may serve as a potential prognostic biomarker and therapeutic target of CRC.

Original languageEnglish (US)
Article number119
JournalJournal of Hematology and Oncology
Volume13
Issue number1
DOIs
StatePublished - Sep 3 2020

Keywords

  • Colorectal cancer
  • Paired organoids
  • Preclinical model
  • SOX2
  • Tumor metastasis

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Modeling tumor development and metastasis using paired organoids derived from patients with colorectal cancer liver metastases'. Together they form a unique fingerprint.

Cite this