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.
MeSH terms
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Antigens, Neoplasm / genetics*
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Antigens, Neoplasm / metabolism
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Biomarkers, Tumor / antagonists & inhibitors
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Biomarkers, Tumor / genetics*
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Biomarkers, Tumor / metabolism
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Breast Neoplasms / blood supply*
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Carcinoma, Ductal, Breast / blood supply*
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Carcinoma, Ductal, Breast / genetics
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Carcinoma, Ductal, Breast / metabolism
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Carcinoma, Ductal, Breast / pathology
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Carcinoma, Lobular / blood supply*
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Carcinoma, Lobular / genetics
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Carcinoma, Lobular / metabolism
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Carcinoma, Lobular / pathology
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism
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Cell Line, Tumor
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Cell Movement
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Coculture Techniques
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Female
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Galectin 3 / metabolism
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Gene Expression Regulation, Neoplastic*
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Gene Knockdown Techniques
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Glycoproteins / antagonists & inhibitors
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Glycoproteins / genetics*
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Glycoproteins / metabolism
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Human Umbilical Vein Endothelial Cells / cytology
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Human Umbilical Vein Endothelial Cells / metabolism
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Humans
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Neovascularization, Pathologic
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Primary Cell Culture
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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RNA, Small Interfering / genetics
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Signal Transduction
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Vascular Endothelial Growth Factor A / genetics*
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Antigens, Neoplasm
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Biomarkers, Tumor
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Carrier Proteins
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Galectin 3
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Glycoproteins
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LGALS3BP protein, human
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RNA, Small Interfering
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt