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Intra-tumoral administration of naked plasmid DNA encoding mouse endostatin inhibits renal carcinoma growth

2001; Wiley; Volume: 91; Issue: 6 Linguagem: Inglês

10.1002/1097-0215(200002)9999

1097-0215

Jaros aw Szary, Stanis aw Szala,

Cell Adhesion Molecules Research

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.