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Galectins and gliomas.

Le Mercier M, Fortin S, Mathieu V, Kiss R, Lefranc F - Brain Pathol. (2009)

Bottom Line: This poor prognosis can be at least partly explained by the fact that glioma cells diffusely infiltrate the brain parenchyma and exhibit decreased levels of apoptosis, and thus resistance to cytotoxic drugs.They are expressed differentially in normal vs. neoplastic tissues and are known to play important roles in several biological processes such as cell proliferation, death and migration.The involvement of these galectins in different steps of glioma malignant progression such as migration, angiogenesis or chemoresistance makes them potentially good targets for the development of new drugs to combat these malignant tumors.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Toxicology; Institute of Pharmacy, Universite Libre de Bruxelles, Brussels, Belgium.

ABSTRACT
Malignant gliomas, especially glioblastomas, are associated with a dismal prognosis. Despite advances in diagnosis and treatment, glioblastoma patients still have a median survival expectancy of only 14 months. This poor prognosis can be at least partly explained by the fact that glioma cells diffusely infiltrate the brain parenchyma and exhibit decreased levels of apoptosis, and thus resistance to cytotoxic drugs. Galectins are a family of mammalian beta-galactoside-binding proteins characterized by a shared characteristic amino acid sequence. They are expressed differentially in normal vs. neoplastic tissues and are known to play important roles in several biological processes such as cell proliferation, death and migration. This review focuses on the role played by galectins, especially galectin-1 and galectin-3, in glioma biology. The involvement of these galectins in different steps of glioma malignant progression such as migration, angiogenesis or chemoresistance makes them potentially good targets for the development of new drugs to combat these malignant tumors.

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Related in: MedlinePlus

Galectins, integrins and cell migration. The interaction of galectins with integrins modulates cell migration as well as other processes. Galectin-1 (Gal-1) interacts with the β1 integrin subunit inducing the phosphorylation of FAK, which modulates cell migration (85). Binding of Gal-1 to integrin is involved in cell adhesion (83). Moreover, Gal-1 was shown to regulate the expression of the protein ADAM-15 that is involved in integrin-mediated adhesion (12). Gal-1 also induces growth inhibition via its interaction with α5β1 (26). This interaction results in the inhibition of the Ras–MEK–ERK pathway and the consecutive transactivation of Sp1, which induces p27 transcription (26). In addition, Gal-1 is involved in the PKCε/vimentin controlled trafficking of integrin β1, a process that is important for cell migration (28). However, it is not known with which molecule(s) Gal-1 is interacting, or in which intra- or extracellular location this interaction is taking place in order to initiate this signaling. Finally, Gal-1 is also involved in cell motility via the Gal-1-induced expression of RhoA and the alteration of the polimerization of the actin cytoskeleton (11) Once again, the receptor to which Gal-1 bind to initiate this signaling is not known. Galectin-3 (Ga-3) regulates cell adhesion via binding to α1β1 (94). Gal-3 also forms a complex with α3β1 and the proteoglycan NG2 (31). This interaction regulates endothelial cell motility and angiogenesis. Finally, Gal-3 has been shown to regulate the expression of integrin α6β1 and actin cytoskeleton organization (20). However, it is not known with which molecule(s) Gal-3 is interacting to initiate this signaling. Galectin-8 (Gal-8) interacts with several integrins including α1β1, α3β1, α5β1 and α6β1. These interactions are involved in cell adhesion and apoptosis (40). Abbreviations: ERK = extracellular signal-regulated kinase; FAK = focal adhesion kinase; MEK = MAP kinase/extracellular signal-regulated kinase kinase (MAPK/ERK Kinase); PKCε = protein kinase C epsilon.
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fig01: Galectins, integrins and cell migration. The interaction of galectins with integrins modulates cell migration as well as other processes. Galectin-1 (Gal-1) interacts with the β1 integrin subunit inducing the phosphorylation of FAK, which modulates cell migration (85). Binding of Gal-1 to integrin is involved in cell adhesion (83). Moreover, Gal-1 was shown to regulate the expression of the protein ADAM-15 that is involved in integrin-mediated adhesion (12). Gal-1 also induces growth inhibition via its interaction with α5β1 (26). This interaction results in the inhibition of the Ras–MEK–ERK pathway and the consecutive transactivation of Sp1, which induces p27 transcription (26). In addition, Gal-1 is involved in the PKCε/vimentin controlled trafficking of integrin β1, a process that is important for cell migration (28). However, it is not known with which molecule(s) Gal-1 is interacting, or in which intra- or extracellular location this interaction is taking place in order to initiate this signaling. Finally, Gal-1 is also involved in cell motility via the Gal-1-induced expression of RhoA and the alteration of the polimerization of the actin cytoskeleton (11) Once again, the receptor to which Gal-1 bind to initiate this signaling is not known. Galectin-3 (Ga-3) regulates cell adhesion via binding to α1β1 (94). Gal-3 also forms a complex with α3β1 and the proteoglycan NG2 (31). This interaction regulates endothelial cell motility and angiogenesis. Finally, Gal-3 has been shown to regulate the expression of integrin α6β1 and actin cytoskeleton organization (20). However, it is not known with which molecule(s) Gal-3 is interacting to initiate this signaling. Galectin-8 (Gal-8) interacts with several integrins including α1β1, α3β1, α5β1 and α6β1. These interactions are involved in cell adhesion and apoptosis (40). Abbreviations: ERK = extracellular signal-regulated kinase; FAK = focal adhesion kinase; MEK = MAP kinase/extracellular signal-regulated kinase kinase (MAPK/ERK Kinase); PKCε = protein kinase C epsilon.

Mentions: Galectins and integrins closely interact when modulating cell adhesion and/or cell migration. For example, Moiseeva et al have shown that galectin-1 interacts with the integrin β1 subunit in vascular smooth muscle cells (85) (Figure 1). Via its direct binding to β1 integrins (without cross-linking), dimeric galectin-1 increases the amount of partially activated β1 integrins, but does not induce dimerization with α subunits (85). In the case of vascular smooth muscle cells, this interaction of galectin-1 with α1β1 integrin has been reported to both transiently phosphorylate focal adhesion kinase and modulate cell attachment, spreading and migration on laminin, but not on cellular fibronectin (38, 85). Thus galectin-1 is likely to affect smooth muscle cell adhesion by interacting with β1 integrin on the cell surface and inducing outside-in signaling (85) (Figure 1).


Galectins and gliomas.

Le Mercier M, Fortin S, Mathieu V, Kiss R, Lefranc F - Brain Pathol. (2009)

Galectins, integrins and cell migration. The interaction of galectins with integrins modulates cell migration as well as other processes. Galectin-1 (Gal-1) interacts with the β1 integrin subunit inducing the phosphorylation of FAK, which modulates cell migration (85). Binding of Gal-1 to integrin is involved in cell adhesion (83). Moreover, Gal-1 was shown to regulate the expression of the protein ADAM-15 that is involved in integrin-mediated adhesion (12). Gal-1 also induces growth inhibition via its interaction with α5β1 (26). This interaction results in the inhibition of the Ras–MEK–ERK pathway and the consecutive transactivation of Sp1, which induces p27 transcription (26). In addition, Gal-1 is involved in the PKCε/vimentin controlled trafficking of integrin β1, a process that is important for cell migration (28). However, it is not known with which molecule(s) Gal-1 is interacting, or in which intra- or extracellular location this interaction is taking place in order to initiate this signaling. Finally, Gal-1 is also involved in cell motility via the Gal-1-induced expression of RhoA and the alteration of the polimerization of the actin cytoskeleton (11) Once again, the receptor to which Gal-1 bind to initiate this signaling is not known. Galectin-3 (Ga-3) regulates cell adhesion via binding to α1β1 (94). Gal-3 also forms a complex with α3β1 and the proteoglycan NG2 (31). This interaction regulates endothelial cell motility and angiogenesis. Finally, Gal-3 has been shown to regulate the expression of integrin α6β1 and actin cytoskeleton organization (20). However, it is not known with which molecule(s) Gal-3 is interacting to initiate this signaling. Galectin-8 (Gal-8) interacts with several integrins including α1β1, α3β1, α5β1 and α6β1. These interactions are involved in cell adhesion and apoptosis (40). Abbreviations: ERK = extracellular signal-regulated kinase; FAK = focal adhesion kinase; MEK = MAP kinase/extracellular signal-regulated kinase kinase (MAPK/ERK Kinase); PKCε = protein kinase C epsilon.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2805916&req=5

fig01: Galectins, integrins and cell migration. The interaction of galectins with integrins modulates cell migration as well as other processes. Galectin-1 (Gal-1) interacts with the β1 integrin subunit inducing the phosphorylation of FAK, which modulates cell migration (85). Binding of Gal-1 to integrin is involved in cell adhesion (83). Moreover, Gal-1 was shown to regulate the expression of the protein ADAM-15 that is involved in integrin-mediated adhesion (12). Gal-1 also induces growth inhibition via its interaction with α5β1 (26). This interaction results in the inhibition of the Ras–MEK–ERK pathway and the consecutive transactivation of Sp1, which induces p27 transcription (26). In addition, Gal-1 is involved in the PKCε/vimentin controlled trafficking of integrin β1, a process that is important for cell migration (28). However, it is not known with which molecule(s) Gal-1 is interacting, or in which intra- or extracellular location this interaction is taking place in order to initiate this signaling. Finally, Gal-1 is also involved in cell motility via the Gal-1-induced expression of RhoA and the alteration of the polimerization of the actin cytoskeleton (11) Once again, the receptor to which Gal-1 bind to initiate this signaling is not known. Galectin-3 (Ga-3) regulates cell adhesion via binding to α1β1 (94). Gal-3 also forms a complex with α3β1 and the proteoglycan NG2 (31). This interaction regulates endothelial cell motility and angiogenesis. Finally, Gal-3 has been shown to regulate the expression of integrin α6β1 and actin cytoskeleton organization (20). However, it is not known with which molecule(s) Gal-3 is interacting to initiate this signaling. Galectin-8 (Gal-8) interacts with several integrins including α1β1, α3β1, α5β1 and α6β1. These interactions are involved in cell adhesion and apoptosis (40). Abbreviations: ERK = extracellular signal-regulated kinase; FAK = focal adhesion kinase; MEK = MAP kinase/extracellular signal-regulated kinase kinase (MAPK/ERK Kinase); PKCε = protein kinase C epsilon.
Mentions: Galectins and integrins closely interact when modulating cell adhesion and/or cell migration. For example, Moiseeva et al have shown that galectin-1 interacts with the integrin β1 subunit in vascular smooth muscle cells (85) (Figure 1). Via its direct binding to β1 integrins (without cross-linking), dimeric galectin-1 increases the amount of partially activated β1 integrins, but does not induce dimerization with α subunits (85). In the case of vascular smooth muscle cells, this interaction of galectin-1 with α1β1 integrin has been reported to both transiently phosphorylate focal adhesion kinase and modulate cell attachment, spreading and migration on laminin, but not on cellular fibronectin (38, 85). Thus galectin-1 is likely to affect smooth muscle cell adhesion by interacting with β1 integrin on the cell surface and inducing outside-in signaling (85) (Figure 1).

Bottom Line: This poor prognosis can be at least partly explained by the fact that glioma cells diffusely infiltrate the brain parenchyma and exhibit decreased levels of apoptosis, and thus resistance to cytotoxic drugs.They are expressed differentially in normal vs. neoplastic tissues and are known to play important roles in several biological processes such as cell proliferation, death and migration.The involvement of these galectins in different steps of glioma malignant progression such as migration, angiogenesis or chemoresistance makes them potentially good targets for the development of new drugs to combat these malignant tumors.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Toxicology; Institute of Pharmacy, Universite Libre de Bruxelles, Brussels, Belgium.

ABSTRACT
Malignant gliomas, especially glioblastomas, are associated with a dismal prognosis. Despite advances in diagnosis and treatment, glioblastoma patients still have a median survival expectancy of only 14 months. This poor prognosis can be at least partly explained by the fact that glioma cells diffusely infiltrate the brain parenchyma and exhibit decreased levels of apoptosis, and thus resistance to cytotoxic drugs. Galectins are a family of mammalian beta-galactoside-binding proteins characterized by a shared characteristic amino acid sequence. They are expressed differentially in normal vs. neoplastic tissues and are known to play important roles in several biological processes such as cell proliferation, death and migration. This review focuses on the role played by galectins, especially galectin-1 and galectin-3, in glioma biology. The involvement of these galectins in different steps of glioma malignant progression such as migration, angiogenesis or chemoresistance makes them potentially good targets for the development of new drugs to combat these malignant tumors.

Show MeSH
Related in: MedlinePlus