Opposite effects of endostatin on different endothelial cells
Annette Schmidt1, Klaus Addicks, Wilhelm Bloch
1Department of Molecular and Cellular Sport Medicine, German Sport University, Carl-Diem-Weg 6, Cologne 50933, Germany.
Abstract:
Endostatin was described as an anti-angiogenic factor. Therefore endostatin looked to be a new way in anti-angiogenic treatment of cancer. Unfortunately, up to now no objective response were seen in clinical trials using endostatin. We compared two different endothelial cell types. Human umbilical vein endothelial cells (HUVEC) and endothelial cells derived from differentiated embryonic stem cells (eESC) were tested in view of endostatin induced proliferation, apoptosis, migration and endostatin binding. Both endothelial cell types had shown an opposite response to endostatin for all observed parameters in dependency of the used concentration. The quantity of HUVEC cells was slightly reduced to 84 +/- 8% by treating with 50 ng/ml endostatin whereas the eESC's showed a significant increase up to 142 +/- 12% under same conditions (p = 0.01). The observation that endostatin is able to evoke non-uniform response for proliferation, cell mount and migration of endothelial cells, with different endostatin binding characteristic, leads to the assumption that endostatin effect is strongly dependent from endothelial cell type. Furthermore the cell biological response at lower concentration on angiogenic eESC gives evidence for an angiogenic modulatory rather than a predicted anti-angiogenic role of endostatin.
Insights
Endostatin
Area of Science:
- Endothelial cell biology
- Cancer research
- Angiogenesis
Background:
- Endostatin was investigated as a potential anti-angiogenic cancer therapy.
- Clinical trials with endostatin have not shown objective responses.
- Endothelial cell type may influence endostatin's efficacy.
Purpose of the Study:
- To compare the effects of endostatin on two distinct endothelial cell types.
- To investigate endostatin's impact on proliferation, apoptosis, migration, and binding.
- To determine if endostatin's role is angiogenic or anti-angiogenic.
Main Methods:
- Comparison of human umbilical vein endothelial cells (HUVEC) and embryonic stem cell-derived endothelial cells (eESC).
- Assessment of endostatin-induced proliferation, apoptosis, migration, and binding.
- Evaluation of dose-dependent responses to endostatin.
Main Results:
- Endothelial cells exhibited opposing responses to endostatin based on cell type and concentration.
- HUVEC proliferation decreased slightly with endostatin, while eESC proliferation significantly increased.
- Endostatin binding characteristics varied between HUVEC and eESC.
Conclusions:
- Endostatin's effect on endothelial cells is highly dependent on the cell type.
- Endostatin may act as an angiogenic modulator rather than an anti-angiogenic agent.
- Further research is needed to understand endostatin's complex role in angiogenesis.
