Publikationsdatum:
2009-11-20
Beschreibung:
Abstract 3047 Poster Board II-1023 Introduction A beneficial effect of low molecular weight heparins (LMWH) on the survival of cancer patients is suggested by clinical data and has been attributed to a broad range of activities, including the capacity to affect the hemostatic and angiogenic properties of endothelial cells. We have previously observed that unfractionated heparin and LMWHs with a mean molecular weight (MW) of 4.5 to 5.7 KDa can effectively antagonise tumor cell-induced angiogenesis in a microvascular endothelium-based Matrigel assay (Marchetti et al, Thromb Res 2008). Aim Since this anti-angiogenic activity of heparins may depend on the mean MW and the composition of their polysaccharidic chains, this study was designed to evaluate the capacity of ‘second generation’ LMWHs, with a lower MW, to counteract the pro-angiogenic stimulus of tumor cells: i.e. the LMWH Bemiparin, that possesses the lowest MW among commercially available LMWH (i.e. 3.6 KDa), and of its ultra low MW derivative RO-14 (MW=2.5 KDa, Laboratorios Farmaceuticos Rovi S.A., Madrid, Spain). Methods Tumor cell conditioned media (TCM) were obtained from three human cell lines of different tumor types, i.e. H69 (small cell lung cancer), MDA.MB.231 (breast cancer), and NB4 (acute promyelocytic leukemia). Human microvascular endothelial cells (HMEC-1) were incubated for 24h in Matrigel with TCM, or purified proangiogenic factors (VEGF, FGF-2), in the absence or presence of increasing concentrations (0.01-0.1-1 IU/ml) of Bemiparin or RO-14. Tubule formation was photographed under inverted microscopy and quantified by an image analysis software. The same heparins were tested for their capacity to counteract endothelial migration elicited by TCM in the wound healing assay. The levels of the pro-angiogenic factors VEGF, FGF-2 and IL-1beta in TCM were quantified by ELISA. Results All three TCM induced a significant (p
Print ISSN:
0006-4971
Digitale ISSN:
1528-0020
Thema:
Biologie
,
Medizin
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