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LGALS3BP, lectin galactoside-binding soluble 3 binding protein, induces vascular endothelial growth factor in human breast cancer cells and promotes angiogenesis

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Abstract

Elevated serum or tissue levels of lectin galactoside-binding soluble 3 binding protein (LGALS3BP) have been associated with short survival and development of metastasis in a variety of human cancers. However, the role of LGALS3BP, particularly in the context of tumor–host relationships, is still missing. Here, we show that LGALS3BP knockdown in MDA-MB-231 human breast cancer cells leads to a decreased adhesion to fibronectin, a reduced transendothelial migration and, more importantly, a reduced expression of vascular endothelial growth factor (VEGF). Production of VEGF, that was restored by exposure of silenced cells to recombinant LGALS3BP, required an intact PI3k/Akt signaling. Furthermore, we show that LGALS3BP was able to directly stimulate HUVEC tubulogenesis in a VEGF-independent, galectin-3-dependent manner. Immunohistochemical analysis of human breast cancer tissues revealed a correlation among LGALS3BP expression, VEGF expression, and blood vessel density. We propose that in addition to its prometastatic role, LGALS3BP secreted by breast cancer cells functions critically as a pro-angiogenic factor through a dual mechanism, i.e by induction of tumor VEGF and stimulation of endothelial cell tubulogenesis.

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Authors and Affiliations

  1. MediaPharma s.r.l., Via Colle dell’Ara, Chieti, Italy

    Enza Piccolo, Nicola Tinari, Sara Traini, Rossana La Sorda, Maurizia D’Egidio, Annalisa Di Risio, Mauro Piantelli, Clara Natoli & Stefano Iacobelli

  2. Department of Biomedical Sciences, “G. d’Annunzio” University and Foundation, Via dei Vestini, 66100, Chieti, Italy

    Enza Piccolo, Nicola Tinari, Daniela Semeraro, Sara Traini, Imma Fichera, Albana Cumashi, Rossana La Sorda, Rossano Lattanzio, Maurizia D’Egidio, Annalisa Di Risio, Mauro Piantelli, Clara Natoli & Stefano Iacobelli

  3. Laboratory of Molecular Pathology, Regina Elena National Cancer Institute, Rome, Italy

    Francesca Spinella & Anna Bagnato

  4. Department of Molecular Biology, Max Planck Institute of Biochemistry, Martinsried/Munich, Germany

    Pavlos Stampolidis & Axel Ullrich

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  1. Enza Piccolo
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  2. Nicola Tinari
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Correspondence to Enza Piccolo.

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Piccolo, E., Tinari, N., Semeraro, D. et al. LGALS3BP, lectin galactoside-binding soluble 3 binding protein, induces vascular endothelial growth factor in human breast cancer cells and promotes angiogenesis. J Mol Med 91, 83–94 (2013). https://doi.org/10.1007/s00109-012-0936-6

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  • DOI: https://doi.org/10.1007/s00109-012-0936-6

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