The role of integrins in the malignant phenotype of gliomas

Uhm, Joon H.; Gladson, Candece L.; Rao, Jasti S.

doi:10.2741/uhm

Cited by 109 publications

(71 citation statements)

References 77 publications

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“…Thereby, the receptor state y is a subcellular scale (microscale) variable and refers to the volume fraction of cell surface receptors bound to insoluble ligands in the surrounding tissue. While it is clear that integrins (a family of heterodimeric cell adhesion molecules playing a crucial role in cell-cell and cell-matrix interaction [32,33,45]) and their binding to the ECM are essential for glioma migration [15,63] and it has been found that glioma cells follow the anisotropic brain structure along the white matter tracts [24,26], the mechanism of adhesion to the myelinated axons is still not elucidated, but integrins do not seem to be responsible for such bindings [24]. In the following we will use the syntagma 'cell surface receptors' for all kinds of receptors involved in cell-tissue adhesion and will concentrate on integrins when referring to chemotherapeutical agents which aim at inhibiting migration and proliferation.…”

Section: Equations On the Mesoscopic And Microscopic Levelsmentioning

confidence: 99%

“…Concerning the treatment we use the idea of reducing tumor cell migration by inhibiting the binding of cell surface receptors to the tissue fibers in the peritumoral region (see e.g., [11,23] and the references therein), hence also rendering the cancer cells more sensitive against radiotherapy, in view of the go-or-grow hypothesis stating that the tumor cells can either migrate or proliferate [9,25,23,29]. On the other hand, however, the receptor binding inhibition can also impair cell proliferation, as the latter is known to be influenced by cell-matrix (and cell-cell) adhesion [14,27,32,40,45,63]; hence, the balance between increasing proliferation through stopping migration and reducing mitotic activity through inhibiting adhesion will be the driving factor for enhancing radiosensitivity. Mathematical models for the therapy of glioma have also been considered in [2,51,52], however in a much simplified monoscale case not able to account for the highly infiltrative behavior of this type of cancer.…”

Section: Introductionmentioning

confidence: 99%

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A Multiscale Modeling Approach to Glioma Invasion with Therapy

Hunt

Surulescu

2016

Vietnam J. Math.

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Section: Equations On the Mesoscopic And Microscopic Levelsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Multiscale Modeling Approach to Glioma Invasion with Therapy

Hunt

Surulescu

2016

Vietnam J. Math.

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“…To induce glioma cell migration, it was necessary to coat the undersurface of the filter with an extracellular matrix (ECM) protein (data not shown). A similar dependence for ECM proteins is thought to occur with glioma cells in vivo (30). We performed our migration assays using laminin, a potent inducer of U251 cell migration (27).…”

Section: B Insets)mentioning

confidence: 99%

Neuregulin-1 Enhances Motility and Migration of Human Astrocytic Glioma Cells

Ritch

Carroll

Sontheimer

2003

Journal of Biological Chemistry

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Gliomas are the most frequently diagnosed adult primary brain malignancy. These tumors have a tendency to invade diffusely into the surrounding healthy brain tissue, thereby precluding their successful surgical removal. In this report, we examine the potential for the neuregulin-1/erbB receptor signaling network to contribute to this process by modulating glioma cell motility. Neuregulin-1 is expressed throughout the immature and adult central nervous system and has been demonstrated to influence the migration of a variety of cell types in the developing brain. In addition, erbB2, an integral member of the heterodimeric neuregulin-1 receptor, has been shown to be overexpressed in human glioma biopsies. Using antibodies specific for erbB2 and erbB3, we show that these receptors localize preferentially in regions of the plasma membrane which are involved in facilitating cellular movement. Here, erbB2 colocalizes and coimmunoprecipitates with members of the focal complex including ␤ 1 -integrin and focal adhesion kinase. Further, erbB receptor activation by neuregulin-1 enhances cell motility in two-dimensional scratch motility assays and stimulates cell invasion in three-dimensional Transwell migration assays. These effects of neuregulin-1 appear to involve the activation of focal adhesion kinase, which occurs downstream from erbB2 receptor stimulation. Taken together these data suggest that neuregulin-1 plays an important modulatory role in glioma cell invasion. Primary brain tumors are derived from the various types of cells of the central nervous system and include gliomas, neuroblastomas, ependymomas, and meningiomas. The most common adult primary brain tumor is the glioma, which is thought to arise from central nervous system glial cells. Of the gliomas, those classified as astrocytic tumors are the most frequently diagnosed (1). Implicit in this classification is the assumption that astrocytic tumors arise from astrocytic glial cells. However, their precise lineage relationship is unknown; it is unclear whether these tumors arise from differentiated astrocytes or from their undifferentiated precursors. Indeed, there are striking similarities between neural precursors and gliomas such as their ability to migrate, often over long distances, through the brain (for review, see Ref.2). Successful surgical treatment of patients diagnosed with a glioma is difficult because of this migratory phenotype. In particular, it is believed that cells at the tumor margin migrate away from their site of origin to colonize distant sites within the brain (3, 4). The molecular mechanisms underlying this aggressive phenotype are poorly understood. However, a number of factors have been implicated in promoting tumor cell invasion. These include the remodeling of the extracellular environment through the secretion of matrix proteases such as matrix metalloprotease-2 (5), the deposition of extracellular matrix proteins such as laminins that facilitate tumor cell migration (6), and the mutation and/or overexpression of growth factor ...

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“…10 Many reports indicate that the invasive and migratory nature of gliomas is a dynamic process related to their ability of binding to the ECM proteins. [11][12][13] Furthermore, immunohistochemical analysis of the border area between normal brain and glioma has shown the presence of interstitial collagen, fibronectin, laminin, and proteoglycans. 14 While in normal brain these proteins are present mainly within capillaries and large blood vessels.…”

Section: Introductionmentioning

confidence: 99%

Altered expression of alpha-dystroglycan subunit in human gliomas

Calogero¹,

Pavoni²,

Gramaglia³

et al. 2006

Cancer Biology & Therapy

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Dystroglycan (DG) is an integral membrane receptor of extracellular matrix proteins, composed of two subunits alpha and beta derived from a common precursor. In brain DG is expressed in neurons, glia limitans, astrocytic endfeet around vessels and endothelial cells. We investigate whether DG may play a role in brain tumors. Western blot and immunofluorescence analysis showed that, while beta-DG subunit was present, the highly glycosylated alpha-DG subunit was strongly reduced in surgically derived human glioblastoma biopsies, in low passage patient-derived cultures and in glioma cell lines, U87MG and A172MG, but not in all glioma cell lines tested. Immunohistochemistry of tumor frozen sections revealed that the loss of a-DG was confined in the tumor area but not around blood vessels. Overexpression of DG decreased the growth rate of the glioma cell lines lacking the highly glycosylated alpha-DG subunit and the colony-forming efficiency. Clonogenic assay in presence of temozolomide showed an additive effect between DG overexpression and drug treatment. Our data suggest that DG may be involved in the progression of primary brain tumors

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The role of integrins in the malignant phenotype of gliomas

Cited by 109 publications

References 77 publications

A Multiscale Modeling Approach to Glioma Invasion with Therapy

A Multiscale Modeling Approach to Glioma Invasion with Therapy

Neuregulin-1 Enhances Motility and Migration of Human Astrocytic Glioma Cells

Altered expression of alpha-dystroglycan subunit in human gliomas

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