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

Int J Cancer. 2001 Mar 15;91(6):835-9. doi: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1123>3.0.co;2-t.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / prevention & control*
  • Collagen / genetics*
  • Collagen Type XVIII
  • DNA / administration & dosage*
  • DNA Primers / chemistry
  • Endostatins
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Therapy
  • Injections, Subcutaneous
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Neovascularization, Pathologic
  • Peptide Fragments / genetics*
  • Plasmids / genetics*
  • Polymerase Chain Reaction
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Collagen Type XVIII
  • DNA Primers
  • Endostatins
  • Peptide Fragments
  • Collagen
  • DNA