Abstract

The goal of this study was to establish a reproducible nude mouse model of liver metastasis and investigate the potential of deploying targeted injectable retroviral vectors for metastatic gastrointestinal cancer. Human cancer cells were injected into the portal vein via an indwelling catheter. The animals were sacrificed at specified time intervals, and the number of tumor nodules was counted in histologic sections of harvested livers. A group of animals received either an extracellular matrix-targeted or a nontargeted retroviral vector bearing a beta-galactosidase gene by portal vein infusion. The number of tumor nodules increased progressively over time at </=50 days post-infusion (r = 0.81; P < 0.0001). Transduction of tumor nodules was observed in the animals that received a matrix-targeted, but not a nontargeted, vector. We have established a reproducible nude mouse model of liver metastasis, and demonstrated the feasibility of gene delivery to metastatic tumor nodules in vivo by portal vein infusions of a matrix-targeted retroviral vector.

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