Transforming Growth Factors β1 (TGF-β1) and TGF-β2 Promote Glioma Cell Migration via Up-Regulation of αVβ3 Integrin Expression

Platten, Michael; Wick, Wolfgang; Wild-Bode, Christine; Aulwurm, Steffen; Dichgans, J.; Weller, Michael

doi:10.1006/bbrc.2000.2176

Cited by 129 publications

(93 citation statements)

References 16 publications

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“…Thus, we examined the potential involvement of integrins in sFRP-mediated inhibition of migration. Integrin a v b 3 has a particular role in glioma cell migration (Paulus and Tonn, 1994;Platten et al, 2000). Flow cytometry failed to disclose a regulation of a v b 3 integrin expression in the process of sFRP-mediated inhibition of migration.…”

Section: Discussionmentioning

confidence: 99%

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Secreted Frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells

et al. 2000

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Cellular resistance to multiple proapoptotic stimuli and invasion of surrounding brain tissue by migrating tumor cells are main obstacles to an e ective therapy for human malignant glioma. Here, we report that the Wnt family of embryonic di erentiation genes modulate growth of malignant glioma cells in vitro and in vivo and inhibit cellular migration in vitro. sFRPs (soluble Frizzled-related proteins) are soluble proteins that bind to Wnt and interfere with Wnt signaling. We ®nd that sFRP-1 and sFRP-2 are produced by the majority of longterm and ex vivo malignant glioma cell lines. Glioma cells that ectopically express sFRPs exhibit increased clonogenicity and enhanced resistance to serum starvation. In contrast, sFRPs do not modulate glioma cell susceptibility to apoptosis induced by the cytotoxic cytokines, CD95 (Fas/APO-1) ligand (CD95L) or Apo2 ligand/tumor necrosis factor-related apoptosisinducing ligand (Apo2L/TRAIL), or various cytotoxic drugs. sFRP-2 strongly promotes the growth of intracranial glioma xenografts in nude mice. In contrast, enhanced expression of sFRPs inhibits the motility of glioma cells in vitro. sFRP-mediated e ects on glioma cells are accompanied by decreased expression and activity of matrix metalloproteinase-2 (MMP-2) and decreased tyrosine phosphorylation of b-catenin. Thus, sFRPs promote survival under non-supportive conditions and inhibit the migration of glioma cells. We suggest that the regulation of these cellular processes involves expression of MMP-2 and tyrosine phosphorylation of bcatenin. These data support a function for Wnt signaling and its modulation by sFRPs in the biology of human gliomas. Oncogene (2000) 19, 4210 ± 4220.

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Section: Discussionmentioning

confidence: 99%

“…We hypothesized that the decreased motility of sFRP transfectants might be caused by changes in integrin receptor expression. Of the integrins, a v b 3 integrin has been identi®ed to play a particular role in gliomas (Paulus and Tonn, 1994;Platten et al, 2000). Flow cytometry did not (Melkonyan et al, 1997).…”

Section: Malignant Glioma Cells Express Sfrpsmentioning

confidence: 99%

Secreted Frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells

et al. 2000

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“…Celladhesion molecules assist in cell migration by mediating cell attachments through hemophilic interactions, and integrins act as essential links between the extracellular environment and cytoskeleton. In glioma brain tumors, TGF-b1 and TGF-b2 stimulate migration of glioma cells by inducing the expression of a5b3 integrins, whereas anti-TGF-b neutralizing antibodies reduce glioma cell migration (Paulus et al 1995;Platten et al 2000;Wick et al 2001). TGF-b1, TGF-b2, and TGF-b3 have also been shown to increase the number and length of neurites .…”

Section: Migration and Axon Guidancementioning

confidence: 99%

TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function

Meyers

Kessler

2017

Cold Spring Harb Perspect Biol

127

107

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“…However, some authors report on TGF-b1-stimulated migration and invasion of glioma cells (Merzak et al, 1994;Platten et al, 2000), and marked inhibition of glioma invasion modulated by TGF-b1-specific antisense oligonucleotides (Paulus et al, 1995) and by RNA interference targeting both TGF-b1 and TGF-b2 was reported (Friese et al, 2004).…”

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confidence: 99%

The role of versican isoforms V0/V1 in glioma migration mediated by transforming growth factor-β2

et al. 2007

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Versican is a large chondroitin sulphate proteoglycan produced by several tumour cell types, including high-grade glioma. The increased expression of certain versican isoforms in the extracellular matrix (ECM) plays a role in tumour cell growth, adhesion and migration. Transforming growth factor-b2 (TGF-b2) is an important modulator of glioma invasion, partially by remodeling the ECM. However, it is unknown whether it interacts with versican during malignant progression of glioma cells. Here, we analysed the effect of TGF-b2 on the expression of versican isoforms. The expression of versican V0/V1 was upregulated by TGF-b2 detected by quantitative polymerase chain reaction and immunoprecipitation, whereas V2 was not induced. Using time-lapse scratch and spheroid migration assays, we observed that the glioma migration rate is significantly increased by exogenous TGF-b2 and inhibited by TGF-b2-specific antisense oligonucleotides. Interestingly, an antibody specific for the DPEAAE region of glycosaminoglycan-b domain of versican was able to reverse the effect of TGF-b2 on glioma migration in a dose-dependent manner. Taken together, we report here that TGF-b2 triggers the malignant phenotype of high-grade gliomas by induction of migration, and that this effect is, at least in part, mediated by versican V0/V1.

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Transforming Growth Factors β1 (TGF-β1) and TGF-β2 Promote Glioma Cell Migration via Up-Regulation of αVβ3 Integrin Expression

Cited by 129 publications

References 16 publications

Secreted Frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells

Secreted Frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells

TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function

The role of versican isoforms V0/V1 in glioma migration mediated by transforming growth factor-β2

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