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Noninvasive visualization of tumor growth in a human colorectal liver metastases xenograft model using bioluminescence in vivo imaging
Authors:Andreas Thalheimer  MD  Doreen Korb  Lars Bönicke  Armin Wiegering  Bettina MühlingSimone S Riedel  PhD  Christoph Thomas Germer  Andreas Beilhack  Stephanie Brändlein  Christoph Otto
Institution:1. Department of General, Visceral, Vascular, and Paediatric Surgery, University Hospital of Würzburg, Würzburg, Germany;2. Experimental Surgery, Experimental Transplantation Immunology, Department of General, Visceral, Vascular, and Paediatric Surgery, University Hospital of Würzburg, Würzburg, Germany;3. Helios Klinikum Wuppertal, Clinic of General and Visceral Surgery, Wuppertal, Germany;4. Institute of Pathology, University of Würzburg, Würzburg, Germany;5. Department of Biochemistry and Molecular Biology, University of Würzburg, Biocenter, Würzburg, Germany;6. IZKF Research Group for Stem Cell Transplantation, Center for Experimental Molecular Medicine, Department of Internal Medicine II, Würzburg, Germany
Abstract:

Background

Bioluminescence imaging (BLI) is an ideal tool for noninvasive, quantitative monitoring of tumor progression/regression in animal models. The effectiveness of different treatment strategies is displayed by an altered intensity of bioluminescence, demonstrating a change of the tumor burden. The aim of this study was to establish a reliable, reproducible colorectal hepatic metastases cancer animal model.

Methods

Cells of the human colon carcinoma cell line HCT-116 Lucpos expressing the firefly luciferase enzyme gene were used. HCT-116 Lucpos cells (2.5 × 106) were injected through the portal vein into the liver of immunoincompetent nude mice. BLI was used to analyze intrahepatic tumor burden and growth kinetic.

Results

HCT-116 Lucpos cells demonstrated a progressive and reproducible growth in the liver after intraportal injection. Four days after injection, the animals were analyzed for tumor growth by BLI, and mice without or too low bioluminescence signals were excluded (between 10% and 20% animals). HCT-116 Lucpos intrahepatic tumors responded successfully to different dosages (5 and 10 mg/kg) of 5-fluorouracil.

Conclusions

BLI is an important tool with many potential advantages for investigators. The measurement of intrahepatic tumor growth by imaging luciferase activity noninvasively provides valuable information on tumor burden and effectiveness of therapy. Thus, the presented intrahepatic metastases model based on the growth of HCT-116 Lucpos cells is suitable for in vivo testing of different cancer therapy strategies.
Keywords:Colorectal carcinoma  Liver metastases  Bioluminescence  Luciferase  In   vivo imaging  Mouse xenograft cancer models
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