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Intra‐tumoral administration of naked plasmid DNA encoding mouse endostatin inhibits renal carcinoma growth
Author(s) -
Szary Jarosław,
Szala Stanisław
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200002)9999:9999<::aid-ijc1123>3.0.co;2-t
Subject(s) - endostatin , transfection , plasmid , biology , angiogenesis , microbiology and biotechnology , in vivo , cancer research , dna , gene , biochemistry
Endostatin is a C‐terminal fragment of collagen XVIII and has potent anti‐angiogenic and anti‐tumor activity. Mouse endostatin‐coding sequences were obtained using PCR and linked to the signal sequence of influenzavirus hemagglutinin. The signal‐sequence endostatin fragment was subcloned into plasmid vectors under the transcriptional control of cytomegalovirus promoter. Murine renal carcinoma (Renca) cells transfected with endostatin‐coding plasmid are shown to secrete full‐length endostatin. Endostatin‐secreting Renca cells demonstrate slower growth in vivo compared to empty vector–transfected cells, but their in vitro growth is unaffected. Anti‐angiogenic activity of secreted endostatin was confirmed in a Matrigel angiogenesis assay in vivo. We report growth inhibition of Renca tumors resulting from intra‐tumoral delivery of plasmid vector encoding secretable endostatin. Elevated local concentrations of endostatin resulted from multiple intra‐tumoral injections of endotoxin‐purified plasmid DNA. Local endostatin levels were high enough to obtain growth arrest of Renca tumors. © 2001 Wiley‐Liss, Inc.