Establishment and Validation of an Orthotopic Metastatic Mouse Model of Colorectal Cancer

Metastases are largely responsible for cancer deaths in solid tumors due to the lack of effective therapies against disseminated disease, and there is an urgent need to fill this gap. This study demonstrates an orthotopic colorectal cancer (CRC) mouse model system to develop spontaneous metastasis i...

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Main Authors:	Rajput, Ashwani, Agarwal, Ekta, Leiphrakpam, Premila, Brattain, Michael G., Chowdhury, Sanjib
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907346/

id	pubmed-4907346
recordtype	oai_dc
spelling	pubmed-49073462016-06-23 Establishment and Validation of an Orthotopic Metastatic Mouse Model of Colorectal Cancer Rajput, Ashwani Agarwal, Ekta Leiphrakpam, Premila Brattain, Michael G. Chowdhury, Sanjib Research Article Metastases are largely responsible for cancer deaths in solid tumors due to the lack of effective therapies against disseminated disease, and there is an urgent need to fill this gap. This study demonstrates an orthotopic colorectal cancer (CRC) mouse model system to develop spontaneous metastasis in vivo and compare its reproducibility against human CRC. IGF1R-dependent GEO human CRC cells were used to study metastatic colonization using orthotopic transplantation procedures and demonstrated robust liver metastasis. Cell proliferation assays were performed both in the orthotopic primary colon and liver metastatic tumors, and human CRC patient's specimen and similar patterns in H&E and Ki67 staining were observed between the orthotopically generated primary and liver metastatic tumors and human CRC specimens. Microarray analysis was performed to generate gene signatures, compared with deposited human CRC gene expression data sets, analyzed by Oncomine, and revealed similarity in gene signatures with increased aggressive markers expression associated with CRC in orthotopically generated liver metastasis. Thus, we have developed an orthotopic mouse model that reproduces human CRC metastasis. This model system can be effective in developing new therapeutic strategies against disseminated disease and could be implemented for identifying genes that regulate the development and/or maintenance of established metastasis. Hindawi Publishing Corporation 2013-04-21 /pmc/articles/PMC4907346/ /pubmed/27340651 http://dx.doi.org/10.1155/2013/206875 Text en Copyright © 2013 Ashwani Rajput et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Rajput, Ashwani Agarwal, Ekta Leiphrakpam, Premila Brattain, Michael G. Chowdhury, Sanjib
spellingShingle	Rajput, Ashwani Agarwal, Ekta Leiphrakpam, Premila Brattain, Michael G. Chowdhury, Sanjib Establishment and Validation of an Orthotopic Metastatic Mouse Model of Colorectal Cancer
author_facet	Rajput, Ashwani Agarwal, Ekta Leiphrakpam, Premila Brattain, Michael G. Chowdhury, Sanjib
author_sort	Rajput, Ashwani
title	Establishment and Validation of an Orthotopic Metastatic Mouse Model of Colorectal Cancer
title_short	Establishment and Validation of an Orthotopic Metastatic Mouse Model of Colorectal Cancer
title_full	Establishment and Validation of an Orthotopic Metastatic Mouse Model of Colorectal Cancer
title_fullStr	Establishment and Validation of an Orthotopic Metastatic Mouse Model of Colorectal Cancer
title_full_unstemmed	Establishment and Validation of an Orthotopic Metastatic Mouse Model of Colorectal Cancer
title_sort	establishment and validation of an orthotopic metastatic mouse model of colorectal cancer
description	Metastases are largely responsible for cancer deaths in solid tumors due to the lack of effective therapies against disseminated disease, and there is an urgent need to fill this gap. This study demonstrates an orthotopic colorectal cancer (CRC) mouse model system to develop spontaneous metastasis in vivo and compare its reproducibility against human CRC. IGF1R-dependent GEO human CRC cells were used to study metastatic colonization using orthotopic transplantation procedures and demonstrated robust liver metastasis. Cell proliferation assays were performed both in the orthotopic primary colon and liver metastatic tumors, and human CRC patient's specimen and similar patterns in H&E and Ki67 staining were observed between the orthotopically generated primary and liver metastatic tumors and human CRC specimens. Microarray analysis was performed to generate gene signatures, compared with deposited human CRC gene expression data sets, analyzed by Oncomine, and revealed similarity in gene signatures with increased aggressive markers expression associated with CRC in orthotopically generated liver metastasis. Thus, we have developed an orthotopic mouse model that reproduces human CRC metastasis. This model system can be effective in developing new therapeutic strategies against disseminated disease and could be implemented for identifying genes that regulate the development and/or maintenance of established metastasis.
publisher	Hindawi Publishing Corporation
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907346/
_version_	1613594490904248320

Establishment and Validation of an Orthotopic Metastatic Mouse Model of Colorectal Cancer

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