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Endothelial progenitor cells as putative targets for angiostatin
1Laboratory of Molecular Biology, NHLBI, NIH, Bethesda, MD 20892-1650, USA.
Abstract:
Angiostatin, a product of the proteolytic cleavage of plasminogen, possesses potent antitumor and antiangiogenic properties in vivo. Studies with cultured endothelial cells suggest that under certain conditions, angiostatin inhibits the migration and proliferation of these cells or, alternatively, increases their rate of apoptosis. In general, the effects of angiostatin have been considerably less potent in vitro than in vivo. One potential explanation for this disparity is that the in vivo target of angiostatin is not the mature endothelial cell. Recently, evidence has accumulated to show that circulating endothelial progenitor cells (EPCs) contribute to neovascularization. In this study, we have isolated EPCs from human subjects and demonstrated that, in contrast to that of mature endothelial cells, the growth of EPCs is exquisitely sensitive to angiostatin. These results suggest that angiostatin and related compounds may exert their biological effects by inhibiting the contribution of EPCs to angiogenesis and not by altering the growth of mature endothelial cells.
Insights
Angiostatin, an anti-cancer agent, effectively inhibits endothelial progenitor cells (EPCs) but not mature endothelial cells. This finding suggests angiostatin targets EPCs to reduce tumor angiogenesis.
Area of Science:
- Oncology
- Cell Biology
- Vascular Biology
Background:
- Angiostatin, derived from plasminogen, exhibits antitumor and antiangiogenic effects in vivo.
- In vitro studies show variable effects of angiostatin on mature endothelial cells, with less potency than observed in vivo.
- A discrepancy exists between angiostatin's in vitro and in vivo efficacy, suggesting a different primary target.
Purpose of the Study:
- To investigate the differential sensitivity of endothelial progenitor cells (EPCs) and mature endothelial cells to angiostatin.
- To explore the role of EPCs as the primary in vivo target of angiostatin's antiangiogenic activity.
Main Methods:
- Isolation of endothelial progenitor cells (EPCs) from human subjects.
- Assessment of angiostatin's effect on the proliferation and survival of isolated EPCs and mature endothelial cells in vitro.
Main Results:
- Endothelial progenitor cells (EPCs) demonstrated exquisite sensitivity to angiostatin.
- Mature endothelial cells showed significantly less sensitivity to angiostatin compared to EPCs.
- Angiostatin's potent effects were primarily observed on EPCs, not mature endothelial cells.
Conclusions:
- Angiostatin exerts its potent antiangiogenic and antitumor effects by inhibiting endothelial progenitor cells (EPCs).
- The biological activity of angiostatin is likely mediated through its action on EPCs, rather than mature endothelial cells.
- This highlights EPCs as a key target for angiostatin-based therapies in cancer treatment.