Original Articles

Molecular Therapy (2004) 9, 650–657; doi: 10.1016/j.ymthe.2004.01.021

Xenograft Models for Liver Metastasis: Relationship between Tumor Morphology and Adenovirus Vector Transduction

Zong-Yi Li1, Shaoheng Ni1, Xiangling Yang2, Nancy Kiviat2 and André Lieber1,2

  1. 1Division of Medical Genetics, Department of Medicine, University of Washington, Box 357720, Seattle, WA 98195, USA
  2. 2Department of Pathology, University of Washington, Box 357720, Seattle, WA 98195, USA

Correspondence: André Lieber, Fax: (206) 685-8675. E-mail: lieber00@u.washington.edu

Received 29 October 2003; Accepted 30 January 2004.

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Abstract

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.

Keywords:

adenovirus, liver, metastases, extracellular matrix, tumor gene therapy, extracellular matrix xenograft tumor models

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