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Mar. Drugs 2017, 15(6), 186; doi:10.3390/md15060186

Crude Fucoidan Extracts Impair Angiogenesis in Models Relevant for Bone Regeneration and Osteosarcoma via Reduction of VEGF and SDF-1

1
Experimental Trauma Surgery, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany
2
MetaPhysiol, Am Römerberg, 55270 Essenheim, Germany
*
Author to whom correspondence should be addressed.
Received: 12 May 2017 / Revised: 13 June 2017 / Accepted: 16 June 2017 / Published: 20 June 2017
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Abstract

The marine origin polysaccharide fucoidan combines multiple biological activities. As demonstrated by various studies in vitro and in vivo, fucoidans show anti-viral, anti-tumor, anti-oxidant, anti-inflammatory and anti-coagulant properties, although the detailed molecular action remains to be elucidated. The aim of the present study is to assess the impact of crude fucoidan extracts, on the formation of vascular structures in co-culture models relevant for bone vascularization during bone repair and for vascularization processes in osteosarcoma. The co-cultures consisted of bone marrow derived mesenchymal stem cells, respectively the osteosarcoma cell line MG63, and human blood derived outgrowth endothelial cells (OEC). The concentration dependent effects on the metabolic activity on endothelial cells and osteoblast cells were first assessed using monocultures of OEC, MSC and MG63 suggesting a concentration of 100 µg/mL as a suitable concentration for further experiments. In co-cultures fucoidan significantly reduced angiogenesis in MSC/OEC but also in MG63/OEC co-cultures suggesting a potential application of fucoidan to lower the vascularization in bone tumors such as osteosarcoma. This was associated with a decrease in VEGF (vascular endothelial growth factor) and SDF-1 (stromal derived factor-1) on the protein level, both related to the control of angiogenesis and furthermore discussed as crucial factors in osteosarcoma progression and metastasis. In terms of bone formation, fucoidan slightly lowered on the calcification process in MSC monocultures and MSC/OEC co-cultures. In summary, these data suggest the suitability of lower fucoidan doses to limit angiogenesis for instance in osteosarcoma. View Full-Text
Keywords: fucoidan; mesenchymal stem cells; outgrowth endothelial cells; co-culture; angiogenesis; bone formation; osteosarcoma; VEGF; SDF-1 fucoidan; mesenchymal stem cells; outgrowth endothelial cells; co-culture; angiogenesis; bone formation; osteosarcoma; VEGF; SDF-1
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wang, F.; Schmidt, H.; Pavleska, D.; Wermann, T.; Seekamp, A.; Fuchs, S. Crude Fucoidan Extracts Impair Angiogenesis in Models Relevant for Bone Regeneration and Osteosarcoma via Reduction of VEGF and SDF-1. Mar. Drugs 2017, 15, 186.

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