Glioma invasionin vitro: regulation by matrix metalloprotease-2 and protein kinase C

Uhm, Joon H.; Dooley, Nora P.; Villemure, Jean Guy; Yong, V. Wee

doi:10.1007/bf00128958

Cited by 133 publications

(121 citation statements)

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“…39 Other studies have demonstrated that high levels of b1 integrin subunit are expressed in glioma cells, 31 and stimulation of the b1 integrin subunit increases the activation of MMP-2, which is the most crucial proteinase in the invasiveness of glioma cells. [40][41][42][43][44] We reported that cells migrating from malignant glioma spheroids can be stained with anti-MMP-2 antibody, despite poor staining of the spheroid itself. 30 We have not fully clarified the biologic mechanism through which glioma cell motility is suppressed by the downregulation of laminin a4 chain expression.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of laminin α4 chain expression inhibits glioma invasionin vitro andin vivo

et al. 2005

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The laminin family is a structural constituent of the extracellular matrix that plays an essential role in promoting the motility of infiltrative tumor cells. We investigated the role of laminin a4 chain, a subset of laminin-8, -9 and -14, in the motile and invasive activities of human glioma cells. All malignant glioma cell lines examined expressed more mRNA for the laminin a4 and b1 chains than for the b2 chain, indicating that these cells predominantly express the laminin-8 isoform. Introducing an antisense oligonucleotide for laminin a4 chain (AS-Ln-a4) into the glioma cells resulted in downregulation of laminin a4 expression. AS-Ln-a4 also significantly suppressed glioma cell adhesion and migration. Furthermore, invasiveness was significantly reduced in cells transfected with AS-Ln-a4 compared to those transfected with the sense oligonucleotide (S-Ln-a4). Indeed, when glioma spheroids were implanted into rat brain slices, AS-Ln-a4-transfected cells failed to invade surrounding normal brain tissues. In addition, intracerebral injection of glioma cells transfected with AS-Ln-a4 into nude mice resulted in the formation of a noninvasive tumor, whereas injection of cells transfected with S-Ln-a4 resulted in diffuse invasion of brain tissue. These results suggest that mainly laminin-8 is essential for the invasive activity of human glioma cells; thus, a novel therapeutic strategy could target this molecule to treat patients with malignant glioma. ' 2005 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Downregulation of laminin α4 chain expression inhibits glioma invasionin vitro andin vivo

et al. 2005

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“…Consistent with this idea, recombinant or over-expressed TIMP-4 had no effect on cellular viability and proliferation (as measured by 3 H-thymidine incorporation and MTT assays, data not shown), but substantially reduced the invasive capacity of glioma cells through Matrigel. Several MMPs have been linked with the invasive behaviour of malignant gliomas, including MMP-2, MMP-9 and MT1-MMP (Saxena et al, 1995;Sawaya et al, 1996;Uhm et al, 1996;Yamamoto et al, 1996;Deryugina et al, 1998;Lampert et al, 1998;Belien et al, 1999;Forsyth et al, 1999;Price et al, 1999;Raithatha et al, 2000). In particular there is growing evidence for involvement of several other members of the MT-MMP family including MT2-MMP (Nakada et al, 1999), MT5-MMP (Llano et al, 1999) and MT6-MMP (Velasco et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Differential expression and localization of TIMP-1 and TIMP-4 in human gliomas

Groft¹,

Muzik²,

Rewcastle

et al. 2001

Br J Cancer

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Studies have suggested that an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may contribute to the malignant phenotype of gliomas. In this study, we have undertaken a detailed analysis of expression of the TIMP family in normal human brain and malignant gliomas at both the mRNA and protein level. Reverse transcription-PCR (RT-PCR) analyses of total RNA from surgical tumour specimens revealed unique expression patterns for the 4 members of the TIMP family, with TIMP-1 and -4 showing positive and negative correlations, respectively, with glioma malignancy. By RT-PCR, TIMP-2 and TIMP-3 expression did not change with tumour grade. In situ hybridization localized TIMP-1 to glial tumour cells and also to the surrounding tumour vasculature. TIMP-4 transcripts were predominantly localized to tumour cells, though minor expression was found in vessels. Recombinant TIMP-4 reduced invasion of U251 glioma cells through Matrigel, and U87 clones overexpressing TIMP-4 showed reduced invasive capacity in vitro. TIMP-4, but not TIMP-1, blocked Membrane Type-1-MMP-mediated progelatinase-A (MMP-2) activation in human umbilical vein endothelial cells. The differential expression and localization of individual TIMPs may contribute to the pathophysiology of human malignant gliomas, particularly with regard to tumour vascularization. © 2001 Cancer Research Campaign http://www.bjcancer.com

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“…Reactive astrocytes are frequently associated with glioma cells in the CNS (Le et al, 2003). Tumor-associated astrocytes have been demonstrated to mediate glioblastoma cell invasion via activation of proMMP2 (Le et al, 2003), a metalloproteinase that plays a critical role in glioma invasion (Uhm et al, 1996). Some reports have identified sonic hedgehog (SHH)-expressing reactive astrocytes to be highly concentrated in the perivascular regions of gliomas.…”

Section: Astrocytes In the Microenvironment Of Brain Tumorsmentioning

confidence: 99%

“…Co-cultures of brainderived human fibroblasts involving interactions with glioblastoma cells induced production and activation of matrix metalloproteinase MMP2, and its activators MT1-MMP and MT2-MMP (Sameshima et al, 2000). These metalloproteinases have all been shown to be involved in the progression of gliomas (Belien et al, 1999;Sawaya et al, 1996;Uhm et al, 1996).…”

Section: Fibroblasts In the Brain Tumor Microenvironmentmentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

687

327

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High-grade brain tumors are heterogeneous with respect to the composition of bona fide tumor cells and with respect to a range of intermingling parenchymal cells. Glioblastomas harbor multiple cell types, some with increased tumorigenicity and stem cell-like capacity. The stem-like cells may be the cells of origin for tumor relapse. However, the tumor-associated parenchymal cells such as vascular cells, microglia, peripheral immune cells, and neural precursor cells also play a vital role in controlling the course of pathology. In this review, we describe the multiple interactions of bulk glioma cells and glioma stem cells with parenchymal cell populations and highlight the pathological impact as well as signaling pathways known for these types of cell-cell communication. The tumor-vasculature not only nourishes glioblastomas, but also provides a specialized niche for these stem-like cells. In addition, microglial cells, which can contribute up to 30% of a brain tumor mass, play a role in glioblastoma cell invasion. Moreover, non-neoplastic astrocytes can be converted into a reactive phenotype by the glioma microenvironment and can then secrete a number of factors which influences tumor biology. The young brain may have the capacity to inhibit gliomagenesis by the endogenous neural precursor cells, which secrete tumor suppressive factors. The factors, pathways, and interactions described in this review provide a new prospective on the cell biology of primary brain tumors, which may ultimately generate new treatment modalities. However, our picture of the multiple interactions between parenchymal and tumor cells is still incomplete. V

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Glioma invasionin vitro: regulation by matrix metalloprotease-2 and protein kinase C

Cited by 133 publications

References 50 publications

Downregulation of laminin α4 chain expression inhibits glioma invasionin vitro andin vivo

Downregulation of laminin α4 chain expression inhibits glioma invasionin vitro andin vivo

Differential expression and localization of TIMP-1 and TIMP-4 in human gliomas

The brain tumor microenvironment

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