Marine drugs, 2017-05, Vol.15 (5), p.134-298
2017
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- Autor(en) / Beteiligte
- Titel
- Assessment of Heparanase-Mediated Angiogenesis Using Microvascular Endothelial Cells: Identification of λ-Carrageenan Derivative as a Potent Anti Angiogenic Agent
- Ist Teil von
- Marine drugs, 2017-05, Vol.15 (5), p.134-298
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2017
- Quelle
- Electronic Journals Library
- Beschreibungen/Notizen
- Heparanase is overexpressed by tumor cells and degrades the extracellular matrix proteoglycans through cleavage of heparan sulfates (HS), allowing pro-angiogenic factor release and thus playing a key role in tumor angiogenesis and metastasis. Here we propose new HS analogs as potent heparanase inhibitors: Heparin as a positive control, Dextran Sulfate, λ-Carrageenan, and modified forms of them obtained by depolymerization associated to glycol splitting (RD-GS). After heparanase activity assessment, 11 kDa RD-GS-λ-Carrageenan emerged as the most effective heparanase inhibitor with an IC of 7.32 ng/mL compared to 10.7 ng/mL for the 16 kDa unfractionated heparin. The fractionated polysaccharides were then tested in a heparanase-rich medium-based in vitro model, mimicking tumor microenvironment, to determine their effect on microvascular endothelial cells (HSkMEC) angiogenesis. As a preliminary study, we identified that under hypoxic and nutrient poor conditions, MCF-7 cancer cells released much more mature heparanase in their supernatant than in normal conditions. Then a Matrigel assay using HSkMEC cultured under hypoxic conditions in the presence (or not) of this heparanase-rich supernatant was realized. Adding heparanase-rich media strongly enhanced angiogenic network formation with a production of twice more pseudo-vessels than with the control. When sulfated polysaccharides were tested in this angiogenesis assay, RD-GS-λ-Carrageenan was identified as a promising anti-angiogenic agent.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1660-3397eISSN: 1660-3397DOI: 10.3390/md15050134Titel-ID: cdi_doaj_primary_oai_doaj_org_article_9b22b5556e01451ea88e693283291388
- Format
- –
- Schlagworte
- Analogs, Angiogenesis, Angiogenesis Inhibitors - pharmacology, anti-angiogenic, Antiangiogenics, Assaying, Blood vessels, Cancer, Carrageenan, Carrageenan - pharmacology, Cell Line, Cell Line, Tumor, Cleavage, Control, Degradation, Depolymerization, Dextran, Dextran sulfate, Endothelial cells, Endothelial Cells - drug effects, Extracellular, Extracellular matrix, Extracellular Matrix - drug effects, Glucuronidase - antagonists & inhibitors, heparanase, Heparin, Heparin - pharmacology, Humans, Hypoxia, Identification, In vitro methods and tests, Inhibitors, Life Sciences, MCF-7 Cells, Media, Metastases, Microvasculature, Mimicry, Mineral nutrients, Neoplasms, Neoplasms - drug therapy, Neovascularization, Pathologic - drug therapy, Network formation, Polysaccharides, Proteoglycans, Saccharides, Splitting, sulfated polysaccharide, Sulfates, Sulphates, Tumor cells, Tumor Microenvironment - drug effects, λ-Carrageenan