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Intramuscular delivery of antiangiogenic genes suppresses secondary metastases after removal of primary tumors.
- Source :
-
Cancer gene therapy [Cancer Gene Ther] 2005 Jan; Vol. 12 (1), pp. 35-45. - Publication Year :
- 2005
-
Abstract
- The success of surgery to remove primary tumors can be compromised by the subsequent outgrowth of metastases. It is recognized that primary tumors secrete antiangiogenic factors that suppress the outgrowth of their daughter metastases. In accord we show here that surgical removal of primary EL-4 lymphomas led to a marked decrease in the levels of circulating angiostatin and endostatin, and promoted the growth of distant nodular tumors. Expression vectors encoding angiostatin and endostatin, formulated with poly-N-vinyl pyrrolidone (PVP), were injected into the tibialis and gastrocnemia muscles, leading to expression of angiostatin and endostatin in muscle fibers. High levels of biologically active exogenous proteins were secreted into the circulation. Intramuscular gene therapy with angiostatin and endostatin plasmids significantly inhibited tumor vascularity and induced tumor cell apoptosis, and thereby suppressed the growth of secondary subcutaneous and disseminated metastatic tumors in the lung and liver. Simultaneous intramuscular delivery of both angiostatin and endostatin plasmids significantly prolonged the survival of mice after removal of primary tumors. These results suggest that intramuscular gene transfer of angiostatin and endostatin might serve as a prophylactic cancer-prevention strategy to combat the recurrence of cancer after surgical resection of primary tumors.
- Subjects :
- Angiostatins biosynthesis
Animals
Endostatins biosynthesis
Genetic Therapy
Genetic Vectors
Humans
Injections, Intramuscular
Liver Neoplasms prevention & control
Liver Neoplasms secondary
Liver Neoplasms veterinary
Lung Neoplasms prevention & control
Lung Neoplasms secondary
Lung Neoplasms veterinary
Male
Mice
Mice, Inbred C57BL
Muscle, Skeletal
Neoplasm Metastasis physiopathology
Plasmids
Transplantation, Heterologous
Angiostatins genetics
Angiostatins pharmacology
Endostatins genetics
Endostatins pharmacology
Gene Transfer Techniques
Lymphoma pathology
Neoplasm Metastasis genetics
Neoplasm Metastasis prevention & control
Neovascularization, Pathologic genetics
Thymus Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0929-1903
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cancer gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 15486558
- Full Text :
- https://doi.org/10.1038/sj.cgt.7700766