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BACKGROUND: Colorectal cancer (CRC) liver metastasis is highly unfavorable for patient outcome and is a leading cause of cancer-related death. Pre-clinical research of CRC liver metastasis predominately utilizes CRC cell lines grown in tissue culture. Here, we demonstrate that CRC liver metastases organoids derived from human specimens recapitulate some aspects of human disease. METHODS: Human CRC liver metastases pathological specimens were obtained following patient consent. Tumor disaggregates were plated and organoids were allowed to expand. CRC markers were identified by immunofluorescence. Stem cell genes were analysed by QPCR and flow cytometry. Response to drug therapy was quantified using time-lapse imaging and MATLAB analysis. RESULTS: Organoids showed global expression of the epithelial marker, EpCAM and the adenocarcinoma marker, CEA CAM1. Flow cytometry analysis demonstrated that organoids express the stem cell surface markers CD24 and CD44. Finally, we demonstrated that CRC liver metastases organoids acquire chemotherapy resistance and can be utilized as surrogates for drug testing. CONCLUSION: These data demonstrate that CRC liver metastases organoids recapitulate some aspects of human disease and may provide an invaluable resource for investigating novel drug therapies, chemotherapy resistance and mechanism of metastasis.

Original publication

DOI

10.1016/j.scr.2018.01.016

Type

Journal article

Journal

Stem Cell Res

Publication Date

03/2018

Volume

27

Pages

109 - 120

Keywords

Chemotherapy resistance, Colorectal cancer, Liver metastasis, Organoid, Cell Proliferation, Cells, Cultured, Colorectal Neoplasms, Flow Cytometry, Humans, Liver Neoplasms, Organoids, Tumor Cells, Cultured