Colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistance
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 o...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2018-03-01
|
Series: | Stem Cell Research |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506118300229 |
id |
doaj-c5c6ee3165a140de940bb8bc4c445a43 |
---|---|
record_format |
Article |
spelling |
doaj-c5c6ee3165a140de940bb8bc4c445a432020-11-24T23:11:29ZengElsevierStem Cell Research1873-50612018-03-0127109120Colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistanceJon N. Buzzelli0Djamila Ouaret1Graham Brown2Philip D. Allen3Ruth J. Muschel4Old Road Research Campus Building, Department of Oncology, University of Oxford, Oxford, UK; Corresponding author.Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, Department of Oncology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UKOld Road Research Campus Building, Department of Oncology, University of Oxford, Oxford, UKOld Road Research Campus Building, Department of Oncology, University of Oxford, Oxford, UKOld Road Research Campus Building, Department of Oncology, University of Oxford, Oxford, UKBackground: 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. Keywords: Organoid, Liver metastasis, Colorectal cancer, Chemotherapy resistancehttp://www.sciencedirect.com/science/article/pii/S1873506118300229 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jon N. Buzzelli Djamila Ouaret Graham Brown Philip D. Allen Ruth J. Muschel |
spellingShingle |
Jon N. Buzzelli Djamila Ouaret Graham Brown Philip D. Allen Ruth J. Muschel Colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistance Stem Cell Research |
author_facet |
Jon N. Buzzelli Djamila Ouaret Graham Brown Philip D. Allen Ruth J. Muschel |
author_sort |
Jon N. Buzzelli |
title |
Colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistance |
title_short |
Colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistance |
title_full |
Colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistance |
title_fullStr |
Colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistance |
title_full_unstemmed |
Colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistance |
title_sort |
colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistance |
publisher |
Elsevier |
series |
Stem Cell Research |
issn |
1873-5061 |
publishDate |
2018-03-01 |
description |
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. Keywords: Organoid, Liver metastasis, Colorectal cancer, Chemotherapy resistance |
url |
http://www.sciencedirect.com/science/article/pii/S1873506118300229 |
work_keys_str_mv |
AT jonnbuzzelli colorectalcancerlivermetastasesorganoidsretaincharacteristicsoforiginaltumorandacquirechemotherapyresistance AT djamilaouaret colorectalcancerlivermetastasesorganoidsretaincharacteristicsoforiginaltumorandacquirechemotherapyresistance AT grahambrown colorectalcancerlivermetastasesorganoidsretaincharacteristicsoforiginaltumorandacquirechemotherapyresistance AT philipdallen colorectalcancerlivermetastasesorganoidsretaincharacteristicsoforiginaltumorandacquirechemotherapyresistance AT ruthjmuschel colorectalcancerlivermetastasesorganoidsretaincharacteristicsoforiginaltumorandacquirechemotherapyresistance |
_version_ |
1725604120239276032 |