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• W1998066319 abstract "Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, ILAngiogenesis is a highly regulated process that is critical for tumor growth and metastasis. Angiogenesis depends on the balance between different molecules released by the host and tumor cells such as vascular endothelial growth factor (VEGF), fibroblast growth factor basic (bFGF), platelet-derived endothelial cell growth factor (PDGF), insulin-like growth factors (IGF-1 and IGF-2) and scatter factor, which are potential targets for development of angiogenesis inhibitor and depend on heparin sulfate for their biological functions. Heparan sulfate is located in cell surface and in the extracellular matrix and plays crucial regulatory roles in some growth factors. For this reason, heparin has been highlighted as a therapeutic agent as well as anticoagulant. In a previous study, we reported new angiogenesis inhibitor, low molecular weight heparin derivative (heparin-taurocholic acid conjugate; LHT-7) and it showed delay of in vivo tumor growth in MDA-MB231 human breast cancer and inhibited phosphorylation of VEGFR2 through the interaction with VEGF in human umbilical vein endothelial cells (HUVECs). In present study, we revealed LHT-7 as multi-targeting agent to several growth factors and on their actions. LHT7 inhibited phosphorylation of VEGFR2 and binding of LHT7 was increased in VEGFR2 over-expressing HEK293 by FACS analysis. In HUVECs, binding of LHT-7 was shown in a dose-dependent manner by FACS analysis and co-localized with VEGFR2 by immunofluorescence. LHT-7 also inhibited vessel formation enhanced by PDGF-bb in matrigel plug assay and phosphorylation of PDGFR-s in human vascular smooth muscle cell (HuVSMC). Binding of LHT-7 was increased in a dose-dependent manner by FACS analysis and decreased in PDGFR-s-siRNA HuVSMC by immunofluorescence. Finally, LHT-7 inhibited phosphorylation of FGFR-1 in HUVECs and binding of LHT-7 was decreased in FGFR-1-siRNA MDA-MB-361. Overall, LHT-7 has inhibitory effect on phosphorylation of growth factors and binding of LHT-7 was increased in a dose-dependent manner but decreased in a growth factor down-regulated cell. Therefore we suggest that LHT7 would target to VEGFR2, PDGFR- s and FGFR-1 and inhibit their angiogenic roles.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2324. doi:1538-7445.AM2012-2324" @default.
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• W1998066319 date "2012-04-15" @default.
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• W1998066319 title "Abstract 2324: LHT-7 as multi-targeting and anti-angiogenic agent to growth factor receptors" @default.
• W1998066319 doi "https://doi.org/10.1158/1538-7445.am2012-2324" @default.
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