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Antiangiogenesis signals by endostatin
1Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. mshichiri.cme@tmd.ac.jp
Summary
Endostatin rapidly down-regulates genes in endothelial cells, inhibiting their migration. This angiogenesis inhibitor
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Endostatin is a known angiogenesis inhibitor.
- The mechanisms of endostatin's action, including its receptor and intracellular signaling, are not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms by which endostatin inhibits angiogenesis.
- To identify the specific cellular processes and genes affected by endostatin.
Main Methods:
- Gene expression profiling of endothelial cells treated with endostatin.
- Assays to assess apoptosis, proliferation, and migration.
- Studies involving c-myc null fibroblasts and endothelial cells with altered c-myc expression.
Main Results:
- Endostatin rapidly down-regulates numerous genes in endothelial cells, including those involved in cell cycle and apoptosis.
- Endostatin does not induce apoptosis or significant growth inhibition under normal conditions.
- Endostatin potently inhibits endothelial cell migration, particularly in microvascular endothelial cells.
- Suppression of c-myc expression is implicated in endostatin's antimigratory effect.
Conclusions:
- Endostatin's anti-angiogenic effect is primarily mediated by potent inhibition of endothelial cell migration.
- The mechanism involves rapid gene down-regulation, partly through suppression of c-myc.
- Endostatin does not primarily act by inducing apoptosis or growth arrest.