Laminin isoforms and their integrin receptors in glioma cell migration and invasiveness: Evidence for a role of α5-laminin(s) and α3β1 integrin

Kawataki, Tomoyuki; Yamane, Tetsu; Naganuma, Hirofumi; Rousselle, Patricia; Andurén, Ingegerd; Tryggvason, Karl; Patarroyo, Manuel Elkín

doi:10.1016/j.yexcr.2007.07.038

Cited by 105 publications

(99 citation statements)

References 46 publications

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“…20 This observation was confirmed and extended to other central nervous system tumors (astrocytoma, meningioma, and neuroblastoma). 21 In addition, as reported in this study and by others, 11,22 glioblastoma cell lines express ␣6 integrin subunit. The only exception is, to our knowledge, the U87 cell line.…”

Section: Discussionsupporting

confidence: 84%

“…Two other integrins, ␣5␤1 and ␣3␤1, have been shown to be implicated in glioma cell adhesion and migration in vitro. 10,11 In addition, the use of ␣5␤1 antagonists reduces glioma cell proliferation in vitro, 10 while ␣3␤1 antagonists inhibited glioma invasion in vivo. 11 The ␣6 integrin subunit associates with ␤1 or ␤4 subunits to form functional heterodimers that selectively bind laminins.…”

mentioning

confidence: 99%

“…10,11 In addition, the use of ␣5␤1 antagonists reduces glioma cell proliferation in vitro, 10 while ␣3␤1 antagonists inhibited glioma invasion in vivo. 11 The ␣6 integrin subunit associates with ␤1 or ␤4 subunits to form functional heterodimers that selectively bind laminins. The ␣6␤4 integrin is essential for the organiza-tion and maintenance of epithelial hemidesmosomes that link the intermediate filaments with the extracellular matrix.…”

mentioning

confidence: 99%

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Expression of Integrin α6β1 Enhances Tumorigenesis in Glioma Cells

Delamarre

Taboubi

Mathieu

et al. 2009

The American Journal of Pathology

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The integrin ␣6␤1 and its main ligand laminin-111 are overexpressed in glioblastoma, as compared with normal brain tissue, suggesting they may be involved in glioblastoma malignancy. To address this question, we stably expressed the ␣6 integrin subunit in the U87 cell line via retroviral-mediated gene transfer. We show that cell surface expression of the ␣6␤1 integrin led to dramatic changes in tumor U87 cell behavior, both in vitro and in vivo. Nude mice receiving either subcutaneous or intracerebral inoculation of ␣6␤1-expressing cells developed substantially more voluminous tumors than mice injected with control cells. The difference in tumor growth was associated with a marked increase in vascularization in response to ␣6␤1 integrin expression and may also be related to changes in the balance between cell proliferation and survival. Indeed, expression of ␣6␤1 enhanced proliferation and decreased apoptosis of U87 cells both in the tumor and in vitro. Additionally, we demonstrate that ␣6␤1 is implicated in glioblastoma cell migration and invasion and that laminin-111 might mediate dissemination of ␣6␤1-positive cells in vivo. Our results highlight for the first time the considerable role of the integrin ␣6␤1 in glioma progression. Malignant brain tumors have an increasing incidence in both children and adults. In adults, the most common type of primary brain tumor, malignant glioma, is considered as one of the deadliest of human cancers. Despite recent advances in both diagnostic modalities and therapeutic strategies, the 5-year survival rate of less than 3% in patients with glioblastoma is among the lowest for all cancers.1 Patients with the most malignant histopathological subtype, glioblastoma, carry the worst prognosis, with median survival rate of less than 1 year, despite aggressive surgery associated with adjuvant radiotherapy and chemotherapy. 1 Glioblastoma are characterized by rapidly dividing cells, high degree of vascularity, invasion into normal brain tissue, and an intense resistance to death-inducing stimuli.2,3 Since integrins, the major family of extracellular matrix (ECM) receptors, are involved in these events, they are one of the most promising molecules to consider for a targeted therapy.Integrins are cell surface transmembrane ␣␤ heterodimers that recognize specific ECM ligands. The combination of ␣ and ␤ subunits, leading to the formation of at least 24 receptors, determines the ligand specificity. 4 Glioblastoma commonly displays enhanced expression of several integrins along with their ECM ligands: ␣v␤3 and ␣v␤5 (tenascin and vitronectin receptors), ␣5␤1 (fibronectin receptor), ␣2␤1 (collagens receptor), and ␣3␤1, ␣6␤4, and ␣6␤1 (laminins receptors).5 Numerous studies have focused on the ␣v integrin family. The integrins ␣v␤3 and ␣v␤5 are markers of glioblastoma malignancy 6 and influence a variety of processes in glioblastoma progression in vivo, including proliferation, apoptosis, and angiogenesis.7 Furthermore, cilengitide, an ␣v␤3 and ␣v␤5 integrins antagonist, extends mouse surviv...

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Section: Discussionsupporting

confidence: 84%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Expression of Integrin α6β1 Enhances Tumorigenesis in Glioma Cells

Delamarre

Taboubi

Mathieu

et al. 2009

The American Journal of Pathology

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“…Surprisingly, anti-␤1 integrin antibody had no effect on C6-HNK-1 migration, whereas the same antibody significantly inhibited migration of parental C6 cells (Fig. 5D) (38). These results suggest that migration of C6-HNK-1 cells is facilitated by interaction of laminin and HNK-1 glycan but is independent of ␤1 integrin-mediated migration signals.…”

Section: Hnk-1-positive C6 Cells Migrate More Slowly On the Laminin Ementioning

confidence: 80%

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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“…Numerous studies have implicated laminins and their receptors in cancer progression [36][37][38][39][40]. Our own investigation revealed a role for LM-511 but not LM-111 or -332 in the regulation of breast cancer metastasis [5,9,16].…”

Section: Discussionmentioning

confidence: 99%

Laminin α5-derived peptides modulate the properties of metastatic breast tumour cells

Kusuma

Anderson

Pouliot

2011

Clin Exp Metastasis

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The basement membrane protein laminin-511 has been implicated in breast cancer progression and metastasis. To identify peptides from LM-511 that modulate the metastatic properties of breast tumours, we screened laminin alpha 5 chain-derived peptides for their ability to promote adhesion of metastatic mammary carcinoma cells. Two selected adhesive peptides, α5A13b (FHVAYVLIKF) from the LN domain and A5G27 (RLVSYNGIIFFLK) from the LG-globular domain, were further characterised for their inhibitory properties against LM-511 activities in vitro and metastasis in vivo. In vitro, these peptides strongly inhibited LM-511-dependent adhesion and migration of highly metastatic 4T1.2 mammary carcinoma cells. In addition, A5G27 but not α5A13b significantly reduced breast tumour cell proliferation and inhibited laminin-511-induced matrix metalloproteinase-9 expression. Surprisingly, despite its potent inhibitory activity in vitro, A5G27 promoted rather than inhibited 4T1.2 experimental pulmonary metastasis in vivo, regardless of its route of administration. Adhesion of 4T1.2 cells to A5G27 was not inhibited by antibodies directed against α6, β1 or β3 integrins or CD44 but was significantly reduced in the presence of heparin suggesting a role for cell surface glycans. Treatment of the cells with α-L-fucosidase but not neuraminidase or heparinase II also partially inhibited cell adhesion to A5G27 and to LM-511 indicating that these interactions are mediated in part via terminal fucosyl residues. Overall, these results show that LMα5 peptides exhibit distinct functional properties in vitro and in vivo and suggest that interactions between the RLVSYNGIIFFLK sequence present in LM-511 and cell surface glycans may regulate LM-511 metastatic properties in vivo.

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Laminin isoforms and their integrin receptors in glioma cell migration and invasiveness: Evidence for a role of α5-laminin(s) and α3β1 integrin

Cited by 105 publications

References 46 publications

Expression of Integrin α6β1 Enhances Tumorigenesis in Glioma Cells

Expression of Integrin α6β1 Enhances Tumorigenesis in Glioma Cells

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

Laminin α5-derived peptides modulate the properties of metastatic breast tumour cells

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