Endostatin cDNA/Cationic liposome complexes as a promising therapy to prevent lung metastases in osteosarcoma: study in a human-like rat orthotopic tumor

• Published in: Molecular therapy Vol. 11; no. 2; pp. 311 - 319
• Main Authors: Dutour, Aurélie, Monteil, Jacques, Paraf, François, Charissoux, Jean Louis, Kaletta, Cortina, Sauer, Birgitta, Naujoks, Kurt, Rigaud, Michel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2005; Elsevier Limited
• Subjects: Angiogenesis; Animals; Bone cancer; Bone surgery; cationic liposomes; Cations - chemistry; Cell growth; Cell Proliferation; Disease Models, Animal; DNA, Complementary - genetics; DNA, Complementary - metabolism; endostatin; Endostatins - genetics; Endostatins - metabolism; Gene therapy; Genetic Therapy; human-like osteosarcoma; Humans; Immunocompetence; Lectins; Liposomes - chemistry; Lung Neoplasms - prevention & control; Lung Neoplasms - secondary; Lungs; Metabolism; metastases prevention; Metastasis; Neoplasm Metastasis - prevention & control; Osteosarcoma - pathology; Peptides; Rats; Tumors; vascular targeting; gene therapy; human-like osteosarcoma; vascular targeting; endostatin; cationic liposomes; metastases prevention
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2004.10.008

Antiangiogenesis or destruction of tumor neovessels is an effective strategy to prevent tumor growth. Endostatin, one of the many inhibitors of angiogenesis that have been discovered, has shown conflicting results in preclinical assays. We studied the therapeutic potential of lipid/DNA complexes consisting of cationic liposomes and an endostatin-coding plasmid (Endo cDNA/CLP) in an orthotopic osteosarcoma model in rats. Empty plasmid without the endostatin gene complexed with cationic liposomes served as control. Animals were treated intravenously three times a week starting on the day tumors were detectable by 18FDG tomoscintigraphy. During treatment, tumor progression was followed by PET scan and angioscintigraphy, and the effects of antivascular therapy on primary tumor, metastases, and tumor vascular density were confirmed by histologic analysis. Our results demonstrate that therapy using Endo cDNA/CLP is associated with pronounced delay in tumor growth. Moreover, it effectively prevented the occurrence of lung metastases, the major reason for bad prognosis and death in osteosarcoma patients. This approach could be used as an adjuvant therapy for osteosarcoma.