title: LGALS3BP, lectin galactoside-binding soluble 3 binding protein, induces vascular endothelial growth factor in human breast cancer cells and promotes angiogenesis.
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.
authors.affiliation: MediaPharma s.r.l., Via Colle dell'Ara, Chieti, Italy. e.piccolo@unich.it
authors.forename: Enza
authors.initials: E
authors.lastname: Piccolo
authors.forename: Nicola
authors.initials: N
authors.lastname: Tinari
authors.forename: Daniela
authors.initials: D
authors.lastname: Semeraro
authors.forename: Sara
authors.initials: S
authors.lastname: Traini
authors.forename: Imma
authors.initials: I
authors.lastname: Fichera
authors.forename: Albana
authors.initials: A
authors.lastname: Cumashi
authors.forename: Rossana
authors.initials: R
authors.lastname: La Sorda
authors.forename: Francesca
authors.initials: F
authors.lastname: Spinella
authors.forename: Anna
authors.initials: A
authors.lastname: Bagnato
authors.forename: Rossano
authors.initials: R
authors.lastname: Lattanzio
authors.forename: Maurizia
authors.initials: M
authors.lastname: D'Egidio
authors.forename: Annalisa
authors.initials: A
authors.lastname: Di Risio
authors.forename: Pavlos
authors.initials: P
authors.lastname: Stampolidis
authors.forename: Mauro
authors.initials: M
authors.lastname: Piantelli
authors.forename: Clara
authors.initials: C
authors.lastname: Natoli
authors.forename: Axel
authors.initials: A
authors.lastname: Ullrich
authors.forename: Stefano
authors.initials: S
authors.lastname: Iacobelli
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D018920:Coculture Techniques; D005260:Female; D037502:Galectin 3 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D009389:Neovascularization, Pathologic; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D016326:Extracellular Matrix Proteins
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D037502:Galectin 3; D006023:Glycoproteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins; C467484:VEGFA protein, human