| Title | Antiangiogenic activity of endostatin inhibits C6 glioma growth. | | Author(s) | Peroulis I, Jonas N, Saleh M | | Institution | Gene Therapy Laboratory, Department of Surgery, The University of Melbourne and The Royal Melbourne Hospital, Parkville, Victoria, Australia. | | Source | Int J Cancer 2002 Feb 20; 97(6):839-45. | | MeSH | Angiogenesis Inhibitors
Animals
Blotting, Western
Brain Neoplasms
Cattle
Cell Division
Collagen
DNA Primers
Endostatins
Endothelium, Vascular
Female
Glioma
Immunoenzyme Techniques
Mice
Mice, Nude
Neoplasm Transplantation
Neovascularization, Pathologic
Peptide Fragments
Rats
Rats, Wistar
Research Support, Non-U.S. Gov't
Reverse Transcriptase Polymerase Chain Reaction
Transfection
Tumor Cells, Cultured
| | Abstract | Angiogenesis is a vital component of the development and progression of many human solid tumors. Glioblastoma multiforme is one of the most highly vascularised class of solid tumors. Thus, we have investigated the potential antitumourigenic activity of endostatin, an angiogenic inhibitor, in the rat C6 glioma model. We have engineered C6 cells that endogenously express mouse endostatin in order to assess the growth of C6 tumors in vivo when endostatin is constitutively expressed. Endostatin secreted by stably transfected C6 cells is biologically active as shown by its inhibition (26%) of bFGF-stimulated proliferation of BAECs in culture. The subcutaneous implantation of endostatin-C6 cells in athymic (nu/nu) mice resulted in a reduced tumor growth rate (90% inhibition) compared to control cell lines throughout the duration of our experiments. Tumor inhibition was associated with a 50% reduction in the number of vessels, which were also smaller in morphology. However, endostatin-C6 tumors were no more necrotic than control tumors. The implantation of endostatin-C6 cells into immunocompetent Wistar rat brains also resulted in reduced tumor volumes (71% inhibition) compared to controls. Tumor cells were sparsely localised along the injection tract but had not formed discrete tumors. Despite the inhibitory response mediated by endostatin on C6 growth, complete tumor inhibition or dormancy was not observed in either the athymic or immunocompetent tumor models. These findings demonstrate that the endogenous expression of endostatin by C6 glioma cells results in a reduced tumor growth rate in vivo that is associated with an inhibition of tumor angiogenesis. Our data suggest that endostatin should be developed as an adjuvant gene therapy for the effective treatment of gliomas. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 11857365 |
|
