title: Advanced Animal Model of Colorectal Metastasis in Liver: Imaging Techniques and Properties of Metastatic Clones.
abstract: Patients with a limited number of hepatic metastases and slow rates of progression can be successfully treated with local treatment approaches1,2. However, little is known about the heterogeneity of liver metastases, and animal models capable of evaluating the development of individual metastatic colonies are needed. Here, we present an advanced model of hepatic metastases that provides the ability to quantitatively visualize the development of individual tumor clones in the liver and estimate their growth kinetics and colonization efficiency. We generated a panel of monoclonal derivatives of HCT116 human colorectal cancer cells stably labeled with luciferase and tdTomato and possessing different growth properties. With a splenic injection followed by a splenectomy, the majority of these clones are able to generate hepatic metastases, but with different frequencies of colonization and varying growth rates. Using the In Vivo Imaging System (IVIS), it is possible to visualize and quantify metastasis development with in vivo luminescent and ex vivo fluorescent imaging. In addition, Diffuse Luminescent Imaging Tomography (DLIT) provides a 3D distribution of liver metastases in vivo. Ex vivo fluorescent imaging of harvested livers provides quantitative measurements of individual hepatic metastatic colonies, allowing for the evaluation of the frequency of liver colonization and the growth kinetics of metastases. Since the model is similar to clinically observed liver metastases, it can serve as a modality for detecting genes associated with liver metastasis and for testing potential ablative or adjuvant treatments for liver metastatic disease.
authors.affiliation: Department of Surgery, The University of Chicago; Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research, The University of Chicago.
authors.forename: Go
authors.initials: G
authors.lastname: Oshima
authors.affiliation: Department of Surgery, The University of Chicago.
authors.forename: Melinda E
authors.initials: ME
authors.lastname: Stack
authors.affiliation: Department of Surgery, The University of Chicago.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Wightman
authors.affiliation: Department of Surgery, The University of Chicago.
authors.forename: Darren
authors.initials: D
authors.lastname: Bryan
authors.affiliation: Department of Surgery, The University of Chicago.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Poli
authors.affiliation: Department of Surgery, The University of Chicago.
authors.forename: Lai
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Surgery, The University of Chicago.
authors.forename: Kinga B
authors.initials: KB
authors.lastname: Skowron
authors.affiliation: Department of Surgery, The University of Chicago.
authors.forename: Abhineet
authors.initials: A
authors.lastname: Uppal
authors.affiliation: Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research, The University of Chicago.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Pitroda
authors.affiliation: Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research, The University of Chicago.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Surgery, The University of Chicago.
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: Posner
authors.affiliation: Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research, The University of Chicago.
authors.forename: Samuel
authors.initials: S
authors.lastname: Hellman
authors.affiliation: Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research, The University of Chicago.
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Weichselbaum
authors.affiliation: Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research, The University of Chicago; n-khodarev@uchicago.edu.
authors.forename: Nikolai N
authors.initials: NN
authors.lastname: Khodarev
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms; D004195:Disease Models, Animal; D045325:HCT116 Cells; D006801:Humans; D021621:Imaging, Three-Dimensional; D008113:Liver Neoplasms; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation