Ectopic Localization of Mitochondrial ATP Synthase: A Target for Anti-Angiogenesis Intervention?
- 1 December 2005
- journal article
- review article
- Published by Springer Science and Business Media LLC in Journal of Bioenergetics and Biomembranes
- Vol. 37 (6), 461-465
- https://doi.org/10.1007/s10863-005-9492-x
Abstract
A receptor for angiostatin was identified on the surface of endothelial cells as F1–F0 ATP synthase (Moser et al., 1999). Proc. Natl. Acad. Sci. U.S.A. 96, 2811–2816. This ectopic ATP synthase catalyzes ATP synthesis and is inhibited by angiostatin over a wide pH range. Endothelial cells grown at normal pH suffer no ill effects from this angiostatin-mediated inhibition of ATP synthase, whereas endothelial cells grown at low, tumor-like extracellular pH cannot maintain a normal intracellular pH and die. Angiostatin inhibits both ATP synthesis and ATP hydrolysis (Moser et al., 2001) and interferes with intracellular pH regulation (Wahl and Grant, 2002; Wahl et al., 2002). Although angiostatin administered intravenously is cleared from the circulation in a matter of minutes, angiostatin-mimetics that are more stable have potential for clinical application. An angiostatin-mimetic activity has recently been observed using a polyclonal antibody against the β catalytic subunit of ATP synthase. In order to explore the mechanism of action of angiostatin and its mimetics, further work needs to be done to evaluate clinical applicability, specificity, and contraindications for this class of therapeutics.Keywords
This publication has 29 references indexed in Scilit:
- An Inhibitor of the F1 Subunit of ATP Synthase (IF1) Modulates the Activity of Angiostatin on the Endothelial Cell SurfacePublished by Elsevier BV ,2005
- A pilot study of thalidomide in patients with progressive metastatic renal cell carcinomaCancer, 2002
- A randomized phase II trial of docetaxel (taxotere) plus thalidomide in androgen-independent prostate cancerSeminars in Oncology, 2001
- New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGFOncogene, 1999
- Mitochondrial-matrix proteins at unexpected locations: are they exported?Trends in Biochemical Sciences, 1999
- Dormancy of micrometastases: Balanced proliferation and apoptosis in the presence of angiogenesis suppressionNature Medicine, 1995
- Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a lewis lung carcinomaCell, 1994
- A novel ligand in lymphocyte-mediated cytotoxicity: expression of the beta subunit of H+ transporting ATP synthase on the surface of tumor cell lines.The Journal of Experimental Medicine, 1994
- Thalidomide is an inhibitor of angiogenesis.Proceedings of the National Academy of Sciences of the United States of America, 1994
- Tumor Angiogenesis: Therapeutic ImplicationsNew England Journal of Medicine, 1971