Table of Contents
ISRN Hepatology
Volume 2013 (2013), Article ID 206875, 9 pages
http://dx.doi.org/10.1155/2013/206875
Research Article

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

1Division of Surgical Oncology, Department of Surgery, MSC 07 4025, University of New Mexico Health Sciences Center, 1 University of New Mexico, Albuquerque, NM 87131-0001, USA
2Eppley Cancer Center, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA

Received 22 January 2013; Accepted 17 March 2013

Academic Editors: A. Kutup, Z.-Z. Lin, and B. Radosevic-Stasic

Copyright © 2013 Ashwani Rajput et al. 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.

Abstract

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.