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- W2024807762 abstract "Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, ILDespite existing aggressive treatment modalities, survival for advanced stage neuroblastoma remains poor with significant long-term illness in disease survivors. Advance stage disease features are associated with tumor vascularity, and as such, angiogenesis inhibitors may prove useful along with current therapies. SPARC (also known as BM-40 or osteonectin), a matricellular protein, is known to inhibit the proliferation and migration of endothelial cells stimulated by growth factors and induces endothelial cell apoptosis. Here, we sought to determine the effect of SPARC on neuroblastoma tumor cell-induced angiogenesis and to decipher the molecular mechanisms involved in angiogenesis inhibition. SPARC overexpression in neuroblastoma cells inhibited neo-vascularization in vivo as determined by the mouse dorsal air sac model. In addition, conditioned medium from SPARC-overexpressed neuroblastoma cancer cells (pSPARC-CM) inhibited endothelial tube formation in vitro. SPARC-overexpressed tumor cell conditioned medium decreased proliferation (as determined by MTT assay and Ki-67 immunofluorescence) and induced apoptosis in endothelial cells (as determined by TUNEL assay). Furthermore, SPARC-overexpressed tumor cell conditioned medium inhibited expression of the pro-angiogenic molecules VEGF, FGF, PDFG, and MMP-9 as determined by human angiogenesis-PCR array. In addition to the inhibition of growth factors, SPARC-overexpressed tumor cell conditioned medium inhibited Notch signaling molecules in HMEC cells as determined by Western blotting. Conditioned medium from neuroblastoma cells overexpressed with Notch intracellular domain after SPARC overexpression, induced growth factors and led to increased tube formation in vitro. In vivo endothelial cell death was confirmed by co-localization studies with TUNEL assay, and an endothelial marker, CD31, in tumor sections from SPARC-overexpressed mice. Our data collectively suggest that SPARC overexpression induces endothelial cell apoptosis in vivo and inhibits angiogenesis both in vitro and in vivo.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 4358. doi:1538-7445.AM2012-4358" @default.
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- W2024807762 date "2012-04-15" @default.
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- W2024807762 title "Abstract 4358: Notch signaling regulates tumor-induced angiogenesis in SPARC-overexpressed neuroblastoma" @default.
- W2024807762 doi "https://doi.org/10.1158/1538-7445.am2012-4358" @default.
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