A Recellularized Human Colon Model Identifies Cancer Driver Genes

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2016 Jul 12

PMID 27398792

Citations 58

Authors

Huanhuan Joyce Chen

Zhubo Wei

Jian Sun

Asmita Bhattacharya

David J Savage

Rita Serda

Yuri Mackeyev

Steven A Curley

Pengcheng Bu

Lihua Wang

Shuibing Chen

Leona Cohen-Gould

Emina Huang

Xiling Shen

Steven M Lipkin

Neal G Copeland

Nancy A Jenkins

Michael L Shuler

Affiliations

Soon will be listed here.

Abstract

Refined cancer models are needed to bridge the gaps between cell line, animal and clinical research. Here we describe the engineering of an organotypic colon cancer model by recellularization of a native human matrix that contains cell-populated mucosa and an intact muscularis mucosa layer. This ex vivo system recapitulates the pathophysiological progression from APC-mutant neoplasia to submucosal invasive tumor. We used it to perform a Sleeping Beauty transposon mutagenesis screen to identify genes that cooperate with mutant APC in driving invasive neoplasia. We identified 38 candidate invasion-driver genes, 17 of which, including TCF7L2, TWIST2, MSH2, DCC, EPHB1 and EPHB2 have been previously implicated in colorectal cancer progression. Six invasion-driver genes that have not, to our knowledge, been previously described were validated in vitro using cell proliferation, migration and invasion assays and ex vivo using recellularized human colon. These results demonstrate the utility of our organoid model for studying cancer biology.

Citing Articles

Advances in the application of colorectal cancer organoids in precision medicine.

Zhang Y, Meng R, Sha D, Gao H, Wang S, Zhou J Front Oncol. 2024; 14:1506606.

PMID: 39697234 PMC: 11653019. DOI: 10.3389/fonc.2024.1506606.

Potential Use of Organoids in Regenerative Medicine.

Septiana W, Pawitan J Tissue Eng Regen Med. 2024; 21(8):1125-1139.

PMID: 39412646 PMC: 11589048. DOI: 10.1007/s13770-024-00672-y.

Advancements in 3D In Vitro Models for Colorectal Cancer.

Vitale S, Calapa F, Colonna F, Luongo F, Biffoni M, De Maria R Adv Sci (Weinh). 2024; 11(32):e2405084.

PMID: 38962943 PMC: 11348154. DOI: 10.1002/advs.202405084.

Current Advances in the Use of Tissue Engineering for Cancer Metastasis Therapeutics.

Katti P, Jasuja H Polymers (Basel). 2024; 16(5).

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Milk fat globule-epidermal growth factor 8 (MFGE8) prevents intestinal fibrosis.

Lin S, Wang J, Mukherjee P, Mao R, West G, Czarnecki D Gut. 2024; 73(7):1110-1123.

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