Evaluation of bioluminescent imaging for noninvasive monitoring of colorectal cancer progression in the liver and its response to immunogene therapy
Maider Zabala (1,4), Pilar Alzuguren (1), Carolina Benavides (2), Julien Crettaz (1), Gloria Gonzalez-Aseguinolaza (1), Carlos Ortiz de Solorzano (2), Manuela Gonzalez-Aparicio (1), Maria Gabriela Kramer (1,5), Jesus Prieto (3) and Ruben Hernandez-Alcoceba (1)
(1) Division of Gene Therapy and Hepatology. CIMA, University of Navarra. Foundation for Applied Medical Research. Av. Pio XII.Pamplona, Spain
(2) Morphology and Imaging Unit. CIMA, University of Navarra. Foundation for Applied Medical Research. Av. Pio XII. Pamplona,Spain
(3) CIBERehd. University Clinic of Navarra. Pamplona, Spain
(4) Institute for Stem Cell Biology and Regenerative Medicine, University of Stanford, 1050 Arastradero Road, Palo Alto, CA, USA
(5) Peter MacCallum Cancer Research Institute, Cancer Immunology Program, St Andrews Place, East Melbourne, 3001 Australia
Bioluminescent imaging (BLI) is based on the detection of light emitted by living cells expressing a luciferase gene. Stable transfection of luciferase in cancer cells and their inoculation into permissive animals allows the noninvasive monitorization of tumor progression inside internal organs. We have applied this technology for the development of a murine model of colorectal cancer involving the liver, with the aim of improving the pre-clinical evaluation of new anticancer therapies.
A murine colon cancer cell line stably transfected with the luciferase gene (MC38Luc1) retains tumorigenicity in immunocompetent C57BL/6 animals. Intrahepatic inoculation of MC38Luc1 causes progressive liver infiltration that can be monitored by BLI. Compared with ultrasonography (US), BLI is more sensitive, but accurate estimation of tumor mass is impaired in advanced stages. We applied BLI to evaluate the efficacy of an immunogene therapy approach based on the liver-specific expression of the proinflammatory cytokine interleukin-12 (IL-12). Individualized quantification of light emission was able to determine the extent and duration of antitumor responses and to predict long-term disease-free survival.
We show that BLI is a rapid, convenient and safe technique for the individual monitorization of tumor progression in the liver. Evaluation of experimental treatments with complex mechanisms of action such as immunotherapy is possible using this technology.
CITATION Mol Cancer. 2009 Jan 7;8:2