DISTINCT GLIOBLASTOMA CELL LOCALIZATION OF INTEGRINS αvβ3 AND αvβ5

Gladson, Candece L.; Wilcox, J. N.; Gillespie, G. Yancey; Cheresh, D A

doi:10.1097/00005072-199305000-00026

Cited by 6 publications

(14 citation statements)

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“…Based on the absence of most adhesive glycoproteins in the brain neuropil and in the malignant astrocytoma extracellular matrix (Pijuan-Thompson et al, 1999;Gladson, 1999), we hypothesized that malignant astrocytoma cells must synthesize one or more new matrix or cell attachment proteins in order to attach and migrate. The evidence to date indicates that malignant astrocytoma cells synthesize OPN and vitronectin (Saitoh et al, 1995;Gladson et al, 1995). Vitronectin promotes malignant astrocytoma cell attachment and migration (Gladson et al, 1995); however the function of OPN in malignant astrocytoma tumors is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…The evidence to date indicates that malignant astrocytoma cells synthesize OPN and vitronectin (Saitoh et al, 1995;Gladson et al, 1995). Vitronectin promotes malignant astrocytoma cell attachment and migration (Gladson et al, 1995); however the function of OPN in malignant astrocytoma tumors is not clear. In other cell types, OPN can also promote cell attachment and migration, as well as cytoskeletal organization, suggesting it can serve as a cell attachment protein (Liaw et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…We are particularly interested in the ability of malignant astrocytomas to remodel their extracellular matrix by secreting matrix proteins, and proteins that promote cell attachment (Gladson and Cheresh, 1991;Gladson et al, 1995;PijuanThompson et al, 1999). The signi®cant mortality associated with malignant astrocytomas is directly attributable to the invasion of the normal brain by the tumor (Russell and Rubenstein, 1989), which requires integrin-mediated attachment and migration of the tumor cells to the extracellular matrix.…”

Section: Introductionmentioning

confidence: 99%

“…Although migration can occur on the existing matrix of the normal brain (reviewed in Gladson, 1999), the tumor cells can actively remodel their extracellular matrix through the synthesis of matrix proteins and cell attachment proteins that promote cell attachment and migration. Malignant astrocytoma cells in vivo exhibit upregulation of at least two such proteins, vitronectin (Gladson and Cheresh, 1991;Gladson et al, 1995) and osteopontin (OPN) (Saitoh et al, 1995). OPN is not expressed in the normal matrix of most tissues, other than mineralized tissues, but it is synthesized by cells in response to various stimuli, and thus is considered to be a cytokine (Denhardt and Noda, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…OPN also promotes cell attachment and migration through its recognition as a ligand by several cell adhesion receptors, e.g., integrins a v b 3 and a v b 5 ; thus, OPN also is considered to be a cell attachment protein (Liaw et al, 1995;Gladson et al, 2000). Integrins a v b 3 and a v b 5 are upregulated on malignant astrocytoma cells in vivo (Gladson et al, 1995), therefore, OPN could potentially promote malignant astrocytoma cell attachment and migration.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional regulation of the human osteopontin promoter: functional analysis and DNA-protein interactions

et al. 2000

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Synthesis of cell attachment proteins and cytokines, such as osteopontin (OPN), can promote tumor cell remodeling of the extracellular matrix into an environment that promotes tumor cell attachment and migration. We investigated the transcriptional regulation of OPN in the U-251MG and U-87MG human malignant astrocytoma cell lines. Deletion and mutagenesis analyses of the OPN promoter region identi®ed a proximal promoter element (724 to 794 relative to the transcription initiation site) that is essential for maintaining high levels of OPN expression in the tumor cells. This element, designated RE-1, consists of two cis-acting elements, RE-1a (755 to 786) and RE-1b (722 to 745), which act synergistically to regulate the activity of the OPN promoter. Gel shift assays using nuclear extracts of U-251MG cells demonstrated that RE-1a contains binding sites for transcription factors Sp1, the glucocorticoid receptor, and the E-box-binding factors, whereas RE-1b contains a binding site for the octamer motif-binding protein (OCT-1/OCT-2). Inclusion of antibodies directed toward Myc and OCT-1 in the gel shift assays indicated that Myc and OCT-1 participate in forming DNAprotein complexes on the RE-1a and RE-1b elements, respectively. Our results identify two previously unrecognized elements in the OPN promoter that act synergistically to promote upregulation of OPN synthesis by tumor cells but are regulated by di erent transcription factors. Oncogene (2000) 19, 5801 ± 5809.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Transcriptional regulation of the human osteopontin promoter: functional analysis and DNA-protein interactions

et al. 2000

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Advances in the Knowledge of the Molecular Biology of Glioblastoma and Its Impact in Patient Diagnosis, Stratification, and Treatment

2020

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Gliomas are the most common primary brain tumors in adults. They arise in the glial tissue and primarily occur in the brain. Low‐grade tumors of World Health Organization (WHO) grade II tend to progress to high‐grade gliomas of WHO grade III and, eventually, glioblastoma of WHO grade IV, which is the most common and deadly glioma, with a median survival of 12–15 months after final diagnosis. Knowledge of the molecular biology and genetics of glioblastoma has increased significantly in the past few years, giving rise to classification methods that can help in management and stratification of glioblastoma patients. However, glioblastoma remains an incurable disease. Glioblastoma cells have acquired genetic and metabolic adaptations in order to sustain tumor growth and progression, including changes in energetic metabolism, invasive capacity, migration, and angiogenesis, that make it very difficult to find suitable therapeutic targets and to develop effective drugs. The current standard of care for glioblastoma patients is surgery followed by radiotherapy plus concomitant and adjuvant chemotherapy with temozolomide. Although progress in glioblastoma therapies in recent years has been more limited than in other tumors, numerous drugs and targets are being proposed and many clinical trials are underway to develop effective subtype‐specific treatments.

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TGF-β1 up-regulates paxillin protein expression in malignant astrocytoma cells: requirement for a fibronectin substrate

et al. 2001

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Cytokines can in¯uence the interactions between members of the integrin cell adhesion receptor family and the extracellular matrix thereby potentially aecting cell function and promoting cell adhesion, growth and migration of malignant astrocytoma tumor cells. As malignant astrocytoma cells synthesize TGF-b1 in vivo, we analysed the eects of TGF-b1 on signaling events associated with integrin receptor ligation, focusing on the eects on paxillin, a phosphorylated adaptor protein, that acts as a scaold for signaling molecules recruited to focal adhesions. TGF-b1-stimulation of primary astrocytes and serum-starved U-251MG malignant astrocytoma cells attached to ®bronectin induced a substantial increase in the levels of paxillin protein (®vefold increase at 2.0 ng/ml) in a dose-and timedependent manner compared to the levels observed on plating onto ®bronectin in the absence of stimulation. In the astrocytoma cells, this resulted in an increase in the pool of tyrosine-phosphorylated paxillin, although it did not appear to alter the extent of phosphorylation of the paxillin molecules. In contrast, in primary astrocytes the protein levels were upregulated in the absence of a parallel increase in phosphorylation. The TGF-b1-stimulated increase in paxillin levels required ligation of the ®bronectin receptor, as it was not induced when the cells were plated onto vitronectin, collagen or laminin. The increase in the pool of paxillin on TGFb1 stimulation of the ®bronectin-plated astrocytoma cells was associated with an increase in translation, but was not associated with an increase in the steady-state levels of paxillin mRNA. Stimulation with TGF-b1 on a ®bronectin substrate increased subsequent attachment and spreading of U-251MG cells onto ®bronectin and, to a lesser extent, vitronectin, but not collagen. Our results indicate that physiologic levels of TGF-b1 stimulate the expression of paxillin protein at the level of translation through a process that requires engagement of the ®bronectin receptor, and promotes attachment and spreading of malignant astrocytoma cells on ®bronectin.Oncogene (2001) 20, 7976 ± 7986.

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DISTINCT GLIOBLASTOMA CELL LOCALIZATION OF INTEGRINS αvβ3 AND αvβ5

Cited by 6 publications

References 0 publications

Transcriptional regulation of the human osteopontin promoter: functional analysis and DNA-protein interactions

Transcriptional regulation of the human osteopontin promoter: functional analysis and DNA-protein interactions

Advances in the Knowledge of the Molecular Biology of Glioblastoma and Its Impact in Patient Diagnosis, Stratification, and Treatment

TGF-β1 up-regulates paxillin protein expression in malignant astrocytoma cells: requirement for a fibronectin substrate

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