Establishment of a nude mouse model of hepatic metastasis for evaluation of targeted retroviral gene delivery.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Stapfer
Maria
M
Department of Surgery (Colorectal), Keck School of Medicine, University of Southern California School of Medicine, Los Angeles, California 90033, USA.
Hu
Jie
J
Wei
Denise
D
Groshen
Susan
S
Beart
Robert W
RW
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D003110:Colonic Neoplasms / Q000473:pathology; D005260:Female; D018390:Gene Targeting / Q000379:methods; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D009362:Neoplasm Metastasis; D009385:Neoplastic Processes; D010190:Pancreatic Neoplasms / Q000473:pathology; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics
D001616:beta-Galactosidase