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Inhibition of induced angiogenesis in a human microvascular endothelial cell line by ET-18-OCH3
F J Candal1, D C Bosse, W R Vogler
1Biological Products Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333.
Abstract:
Alkyl-lysophospholipids are a group of anti-cancer compounds that have previously been shown to have the unique feature of being selectively toxic to neoplastic tissues. One of these compounds, ET-18-OCH3, has been used for purging bone marrow of cancer cells in phase I clinical trials. Tumor-induced angiogenesis has been directly correlated with tumor growth and metastasis. In this study, we examined the effect ET-18-OCH3 has on a human microvascular endothelial cell line (HMEC-1), including the following functions: angiogenesis, cell-adhesion molecule expression, and cell-junction integrity. We found that ET-18-OCH3 (in vitro) reversibly inhibited induced angiogenesis at levels that did not affect viability. At lower concentrations, ET-18-OCH3 down-regulated the expression of cell-adhesion molecules and affected the integrity of cell-to-cell junctions. This observation demonstrates this versatile family of compounds to have additional targets of action.
Insights
Alkyl-lysophospholipids like ET-18-OCH3 show anti-cancer properties by selectively targeting tumor cells. This study reveals ET-18-OCH3 also inhibits angiogenesis and affects endothelial cell junctions without impacting cell viability.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Alkyl-lysophospholipids are anti-cancer agents selectively toxic to neoplastic tissues.
- ET-18-OCH3, an alkyl-lysophospholipid, has been utilized in clinical trials for bone marrow purging.
- Tumor angiogenesis is crucial for tumor growth and metastasis.
Purpose of the Study:
- To investigate the effects of ET-18-OCH3 on human microvascular endothelial cells (HMEC-1).
- To assess the impact of ET-18-OCH3 on angiogenesis, cell-adhesion molecule expression, and cell-junction integrity in HMEC-1 cells.
Main Methods:
- In vitro study using a human microvascular endothelial cell line (HMEC-1).
- Evaluation of ET-18-OCH3's effects on induced angiogenesis.
- Analysis of cell-adhesion molecule expression and cell-junction integrity following ET-18-OCH3 treatment.
Main Results:
- ET-18-OCH3 reversibly inhibited induced angiogenesis in HMEC-1 cells at non-cytotoxic concentrations.
- Lower concentrations of ET-18-OCH3 down-regulated cell-adhesion molecule expression.
- ET-18-OCH3 treatment affected the integrity of cell-to-cell junctions in HMEC-1 cells.
Conclusions:
- ET-18-OCH3 exhibits anti-angiogenic properties.
- ET-18-OCH3 impacts endothelial cell adhesion and junctional integrity.
- Alkyl-lysophospholipids possess multiple mechanisms of action against cancer, including effects on angiogenesis and endothelial cell function.