Xenograft models for liver metastasis: Relationship between tumor morphology and adenovirus vector transduction.
The improvement of initial tumor cell transduction with viral vectors is a major task in tumor gene therapy. We have developed mouse tumor models with hepatic metastases to study transduction of tumor cells after systemic adenovirus vector application. The tumor models were established by intraportal transplantation of human tumor cell lines into immunodeficient mice. Liver metastases derived from cervix, colon, breast, and liver cancer lines were analyzed for distribution of extracellular matrix, vascularization, and transgene expression after tail vein injection of adenovirus vectors. Overall, xenografts resembled the morphology of corresponding tumors in cancer patients. Adenovirus-mediated gene delivery depended on tumor vascularization and direct contact between blood vessels and tumor cells. These models represent important tools for studying and improving tumor gene therapy approaches.
Li
Zong-Yi
ZY
Division of Medical Genetics, Department of Medicine, University of Washington, Box 357720, Seattle, WA 98195, USA.
Ni
Shaoheng
S
Yang
Xiangling
X
Kiviat
Nancy
N
Lieber
André
A
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002277:Carcinoma / Q000473:pathology / Q000556:secondary; D018270:Carcinoma, Ductal, Breast / Q000473:pathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007120:Immunochemistry; D007797:Laminin / Q000276:immunology; D008113:Liver Neoplasms / Q000473:pathology* / Q000556:secondary*; D051379:Mice; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D001616:beta-Galactosidase / Q000276:immunology
D000906:Antibodies; D007797:Laminin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D001616:beta-Galactosidase