Polysialic Acid Neural Cell Adhesion Molecule (PSA-NCAM) is an adverse prognosis factor in glioblastoma, and regulates olig2 expression in glioma cell lines

Amoureux, Marie‐Claude; Coulibaly, Boubacar; Chinot, Olivier; Loundou, Anderson; Métellus, Philippe; Rougon, Geneviève; Figarella‐Branger, Dominique

doi:10.1186/1471-2407-10-91

Cited by 89 publications

(73 citation statements)

References 48 publications

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“…Notably, this correlation is observed regardless of histological grade of astrocytic tumor. Previously, it was reported that polysialic acid expression is highly correlated with a poor prognosis of astrocytoma (31,(43)(44)(45). These combined results indicate that HNK-1 glycan expression is an efficient and favorable prognosis marker for patients with astrocytoma.…”

Section: Discussionsupporting

confidence: 53%

HNK-1 Glycan Functions as a Tumor Suppressor for Astrocytic Tumor

Suzuki-Anekoji

Suzuki

Kobayashi

et al. 2011

Journal of Biological Chemistry

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Astrocytic tumor is the most prevalent primary brain tumor. However, the role of cell surface carbohydrates in astrocytic tumor invasion is not known. In a previous study, we showed that polysialic acid facilitates astrocytic tumor invasion and thereby tumor progression. Here, we examined the role of HNK-1 glycan in astrocytic tumor invasion. A Kaplan-Meier analysis of 45 patients revealed that higher HNK-1 expression levels were positively associated with increased survival of patients. To determine the role of HNK-1 glycan, we transfected C6 glioma cells, which lack HNK-1 glycan expression, with ␤1,3-glucuronyltransferase-P cDNA, generating HNK-1-positive cells. When these cells were injected into the mouse brain, the resultant tumors were 60% smaller than tumors emerging from injection of the mock-transfected HNK-1-negative C6 cells. HNK-1-positive C6 cells also grew more slowly than mocktransfected C6 cells in anchorage-dependent and anchorage-independent assays. C6-HNK-1 cells migrated well after treatment of anti-␤1 integrin antibody, whereas the same treatment inhibited cell migration of mock-transfected C6 cells. Similarly, ␣-dystroglycan containing HNK-1 glycan is different from those containing the laminin-binding glycans, supporting the above conclusion that C6-HNK-1 cells migrate independently from ␤1-integrin-mediated signaling. Moreover, HNK-1-positive cells exhibited attenuated activation of ERK 1/2 compared with mock-transfected C6 cells, whereas focal adhesion kinase activation was equivalent in both cell types. Overall, these results indicate that HNK-1 glycan functions as a tumor suppressor.HNK-1 glycan is a glucuronylated and sulfated carbohydrate expressed in a cell type-specific manner (1). HNK-1 glycan was originally characterized as an epitope recognized by a monoclonal antibody raised against human natural killer cells (2). The structure of HNK-1 glycan-positive glycolipid was identified as SO 3 3glucuronic acid ␤133Gal␤134GlcNAc␤133 Gal␤13 4Glc␤13ceramide (3). HNK-1 glycan SO 3 33GlcA␤133Gal is unique and is expressed on both glycolipids (4, 5), N-glycans, and O-glycans (1, 6 -8). HNK-1 glycans have been found on several cell adhesion molecules, including the neural cell adhesion molecule (NCAM), 3 myelin-associated glycoprotein, contactin, P0, GluR2, RPTP␤, and CD24 (9 -14). In humans and rats, HNK-1 glycan is found on migrating neural crest cells, cerebellar neurons, Schwann cells, and myelinated motor neurons. Neurite outgrowth of mouse motor neurons is facilitated by an HNK-1 glycolipid substratum. Similarly, neurite outgrowth is inhibited by HNK-1 glycan but not by non-sulfated HNK-1 precursor glycan (15, 16). These results indicate that sulfated HNK-1 glycan plays a critical role in cell-cell interaction and in cell migration.HNK-1 glycan is sequentially synthesized by two enzymes. The ␤1,3-glucuronyltransferase 1 (GlcAT-P, B3gat1) add ␤1,3-linked glucuronic acid (GlcA) to galactose (17), followed by addition of 3-sulfate to GlcA by the HNK-1 sulfotransferase (HNK-1ST, Chst10) (18...

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Section: Discussionsupporting

confidence: 53%

HNK-1 Glycan Functions as a Tumor Suppressor for Astrocytic Tumor

Suzuki-Anekoji

Suzuki

Kobayashi

et al. 2011

Journal of Biological Chemistry

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“…NCAM over-expression in tumour astrocytes leads to a significant decrease in their invasive behaviour (Edvardsen et al, 1994;Owens et al, 1998), whereas addition of polysialylated acid (PSA) on NCAM has been shown to facilitate glioma invasion (Suzuki et al, 2005). Finally, PSA-NCAM has been recently proposed as a biomarker for the prognosis of patients with glioblastomas (Amoureux et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

N-cadherin expression level modulates integrin-mediated polarity and strongly impacts on the speed and directionality of glial cell migration

Camand

Péglion

Osmani

et al. 2012

Journal of Cell Science

123

107

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SummaryPerturbation of cell polarity is a hallmark of cancer cells. In carcinomas, loss of epithelial E-cadherin contributes to the loss of cell polarity and promotes epithelial-mesenchymal transition and carcinoma infiltration. However, the contribution of classical cadherins to the development of non-epithelial tumours is less well documented. We investigated the impact of the level of N-cadherin expression on the polarity and migration of normal and tumour glial cells. Low levels of N-cadherin were frequently observed in human glioma samples and purified glioma cells. Using a wound-healing assay, we show that a decreased level of N-cadherin promotes a faster and less-directed migration both in normal and tumour cells. N-cadherin-mediated contacts control cell velocity and polarity through the regulation of focal adhesions. In cells expressing low levels of N-cadherin, small focal adhesions are present at the entire cell periphery of confluent cells and are not affected by wounding of the cell monolayer. Under these conditions, wound-induced integrin-mediated recruitment of the small GTPase Cdc42, activation of the Cdc42-mediated polarity pathway and centrosome reorientation do not occur. Re-expression of N-cadherin in gliomas restores cell polarity and strongly reduces cell velocity, suggesting that loss of N-cadherin could contribute to the invasive capacity of tumour astrocytes.

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“…PolySia, therefore, is confined to a small subset of proteins, with NCAM being by far the most abundant carrier of polySia in most mammalian cells (Colley, 2010;Galuska et al, 2010;Hildebrandt et al, 2010). Although polySia is diminished in the majority of tissues during development, various tumours are known to re-express polySia on NCAM and high polySia levels have been correlated with malignant potential and poor prognosis of small cell lung carcinoma, neuroblastoma, glioblastoma, medulloblastoma and rhabdomyosarcoma (Scheidegger et al, 1994;Figarella-Branger et al, 1996;Glüer et al, 1998a;Glüer et al, 1998b;Hildebrandt et al, 1998;Tanaka et al, 2000;Daniel et al, 2001;Amoureux et al, 2010). In the developing nervous system, polySia is crucially involved in the migration of neuronal precursors (Ono et al, 1994;Hu et al, 1996;Chazal et al, 2000;Weinhold et al, 2005;Angata et al, 2007;Burgess et al, 2008) and modulates the responsiveness of oligodendrocyte precursor to chemotactic migration cues (BarralMoran et al, 2003;Zhang et al, 2004;Glaser et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Polysialic acid controls NCAM signals at cell–cell contacts to regulate focal adhesion independent from FGF receptor activity

Eggers

Werneburg

Schertzinger

et al. 2011

Journal of Cell Science

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SummaryThe polysialic acid (polySia) modification of the neural cell adhesion molecule NCAM is a key regulator of cell migration. Yet its role in NCAM-dependent or NCAM-independent modulation of motility and cell-matrix adhesion is largely unresolved. Here, we demonstrate that loss of polySia attenuates tumour cell migration and augments the number of focal adhesions in a cell-cell contact-and NCAM-dependent manner. In the presence or absence of polySia, NCAM never colocalised with focal adhesions but was enriched at cell-cell contacts. Focal adhesion of polySia-and NCAM-negative cells was enhanced by incubation with soluble NCAM or by removing polySia from heterotypic contacts with polySia-NCAM-positive cells. Focal adhesion was compromised by the src-family kinase inhibitor PP2, whereas loss of polySia or exposure to NCAM promoted the association of p59Fyn with the focal adhesion scaffolding protein paxillin. Unlike other NCAM responses, NCAM-induced focal adhesion was not prevented by inhibiting FGF receptor activity and could be evoked by NCAM fragments comprising immunoglobulin domains three and four but not by the NCAM fibronectin domains alone or by an NCAM-derived peptide known to interact with and activate FGF receptors. Together, these data indicate that polySia regulates cell motility through NCAM-induced but FGF-receptor-independent signalling to focal adhesions.

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Polysialic Acid Neural Cell Adhesion Molecule (PSA-NCAM) is an adverse prognosis factor in glioblastoma, and regulates olig2 expression in glioma cell lines

Cited by 89 publications

References 48 publications

HNK-1 Glycan Functions as a Tumor Suppressor for Astrocytic Tumor

HNK-1 Glycan Functions as a Tumor Suppressor for Astrocytic Tumor

N-cadherin expression level modulates integrin-mediated polarity and strongly impacts on the speed and directionality of glial cell migration

Polysialic acid controls NCAM signals at cell–cell contacts to regulate focal adhesion independent from FGF receptor activity

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