Modeling tumor development and metastasis using paired organoids derived from patients with colorectal cancer liver meta
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(2020) 13:119
LETTER TO THE EDITOR
Open Access
Modeling tumor development and metastasis using paired organoids derived from patients with colorectal cancer liver metastases He Li1,2†, Weixing Dai3,4†, Xi Xia1†, Renjie Wang3,4†, Jing Zhao1,2, Lingyu Han3,4, Shaobo Mo3,4, Wenqiang Xiang3,4, Lin Du1, Guangya Zhu1, Jingjing Xie1, Jun Yu5, Nan Liu1, Mingzhu Huang4,6*, Jidong Zhu1,7* and Guoxiang Cai3,4*
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. Keywords: Colorectal cancer, Tumor metastasis, Preclinical model, Paired organoids, SOX2 To the Editor, Tumor heterogeneity plays a key role in cancer progression and therapy resistance [1]. However, knowledge of how tumor heterogeneity arises and contributes to disease progression is still limited [2]. Recent advances in organoid culture have been successfully established in a variety of solid tumors [3–5]. * Correspondence: [email protected]; [email protected]; [email protected] † He Li, Weixing Dai, Xi Xia and Renjie Wang contributed equally to this work. 4 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 1 Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China 3 Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China Full list of author information is available at the end of the article
Tumor organoids retain the histological complexity and genetic heterogeneity of parental tumors, even after many passages [6], providing a wide range of applications for cancer research. Organoids have enormous potential for the identification of optimal treatment strategies in individual patients [6]. For example, human CRC organoids derived from primary tumors [5] and liver metastases [7] have been reported as precision medical models for assessing drug responses. However, paired organoids have not been studied as a model for CRC progression. In the present study, we used paired organoids derived from prima
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