Advanced Animal Model of Colorectal Metastasis in Liver: Imaging Techniques and Properties of Metastatic Clones

Go Oshima, Melinda E. Stack, Sean C. Wightman, Darren Bryan, Elizabeth Poli, Lai Xue, Kinga B. Skowron, Abhineet Uppal, Sean P. Pitroda, Xiaona Huang, Mitchell C. Posner, Samuel Hellman, Ralph R. Weichselbaum, Nikolai N. Khodarev

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
JournalJournal of visualized experiments : JoVE
Issue number117
DOIs
Publication statusPublished - 2016 Nov 30
Externally publishedYes

Fingerprint

Liver
Animals
Animal Models
Clone Cells
Neoplasm Metastasis
Imaging techniques
Growth kinetics
Growth
Luciferases
Tomography
Tumors
Splenectomy
Genes
Cells
Derivatives
Liver Diseases
Colorectal Neoplasms
Testing
Injections
Therapeutics

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Advanced Animal Model of Colorectal Metastasis in Liver : Imaging Techniques and Properties of Metastatic Clones. / Oshima, Go; Stack, Melinda E.; Wightman, Sean C.; Bryan, Darren; Poli, Elizabeth; Xue, Lai; Skowron, Kinga B.; Uppal, Abhineet; Pitroda, Sean P.; Huang, Xiaona; Posner, Mitchell C.; Hellman, Samuel; Weichselbaum, Ralph R.; Khodarev, Nikolai N.

In: Journal of visualized experiments : JoVE, No. 117, 30.11.2016.

Research output: Contribution to journalArticle

Oshima, G, Stack, ME, Wightman, SC, Bryan, D, Poli, E, Xue, L, Skowron, KB, Uppal, A, Pitroda, SP, Huang, X, Posner, MC, Hellman, S, Weichselbaum, RR & Khodarev, NN 2016, 'Advanced Animal Model of Colorectal Metastasis in Liver: Imaging Techniques and Properties of Metastatic Clones', Journal of visualized experiments : JoVE, no. 117. https://doi.org/10.3791/54657
Oshima, Go ; Stack, Melinda E. ; Wightman, Sean C. ; Bryan, Darren ; Poli, Elizabeth ; Xue, Lai ; Skowron, Kinga B. ; Uppal, Abhineet ; Pitroda, Sean P. ; Huang, Xiaona ; Posner, Mitchell C. ; Hellman, Samuel ; Weichselbaum, Ralph R. ; Khodarev, Nikolai N. / Advanced Animal Model of Colorectal Metastasis in Liver : Imaging Techniques and Properties of Metastatic Clones. In: Journal of visualized experiments : JoVE. 2016 ; No. 117.
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