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

Enza Piccolo, Nicola Tinari, Daniela Semeraro, Sara Traini, Imma Fichera, Albana Cumashi, Rossana La Sorda, Francesca Spinella, Anna Bagnato, Rossano Lattanzio, Maurizia D'Egidio, Annalisa Di Risio, Pavlos Stampolidis, Mauro Piantelli, Clara Natoli, Axel Ullrich, Stefano Iacobelli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)83-94
Number of pages12
JournalJournal of Molecular Medicine
Volume91
Issue number1
DOIs
Publication statusPublished - Jan 2013

Keywords

  • Angiogenesis
  • Extracellular matrix
  • Galectin-3
  • LGALS3BP
  • VEGF

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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  • Cite this

    Piccolo, E., Tinari, N., Semeraro, D., Traini, S., Fichera, I., Cumashi, A., La Sorda, R., Spinella, F., Bagnato, A., Lattanzio, R., D'Egidio, M., Di Risio, A., Stampolidis, P., Piantelli, M., Natoli, C., Ullrich, A., & Iacobelli, S. (2013). LGALS3BP, lectin galactoside-binding soluble 3 binding protein, induces vascular endothelial growth factor in human breast cancer cells and promotes angiogenesis. Journal of Molecular Medicine, 91(1), 83-94. https://doi.org/10.1007/s00109-012-0936-6