Inhibition of metastatic tumor growth in nude mice by portal vein infusions of matrix-targeted retroviral vectors bearing a cytocidal cyclin G1 construct

Tumor invasion and associated angiogenesis evoke a remodeling of extracellular matrix components. Retroviral vectors bearing auxiliary matrix-targeting motifs (ie., collagen-binding polypeptides) accumulate at sites of newly exposed collagen, thus promoting tumor site-specific gene delivery. In this...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2000-07, Vol.60 (13), p.3343-3347
Main Authors: GORDON, E. M, PENG XUAN LIU, ZHEN HAI CHEN, LING LIU, WHITLEY, M. D, GEE, C, GROSHEN, S, HINTON, D. B, BEART, R. W, HALL, F. L
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Biological and medical sciences
Cell Line
Cyclin G
Cyclin G1
Cyclins - genetics
Cyclins - physiology
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Genetic Therapy
Genetic Vectors
Humans
Infusions, Intravenous
Liver Neoplasms - pathology
Liver Neoplasms - prevention & control
Liver Neoplasms - secondary
Medical sciences
Mice
Mice, Nude
Pancreatic Neoplasms - pathology
Pancreatic Neoplasms - therapy
Portal Vein
Retroviridae
Tumors. Hypoglycemia
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Summary:Tumor invasion and associated angiogenesis evoke a remodeling of extracellular matrix components. Retroviral vectors bearing auxiliary matrix-targeting motifs (ie., collagen-binding polypeptides) accumulate at sites of newly exposed collagen, thus promoting tumor site-specific gene delivery. In this study, we assessed the antitumor effects of serial portal vein infusions of matrix-targeted vectors bearing a mutant cyclin G1 (dnG1) construct in a nude mouse model of liver metastasis. The size of tumor foci was dramatically reduced in dnG1 vector-treated mice compared with that in control vector- or PBS-treated animals (P = 0.0002). These findings represent a definitive advance in the development of targeted injectable vectors for metastatic cancer.
ISSN:0008-5472
1538-7445