Suppression of matrix metalloproteinase-2 gene expression and invasion in human glioma cells by MMAC/PTEN

Koul, Dimpy; Parthasarathy, R.; Shen, Ruijun; Davies, Michael A.; Jasser, Samar A.; Chintala, Shravan K.; Rao, Jasti S.; Sun, Yaru; Benvenisite, Etty N.; Liu, Ta Jën; Yung, W. K. Alfred

doi:10.1038/sj.onc.1204799

Cited by 104 publications

(71 citation statements)

References 45 publications

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“…Also, cell movement, which is necessary for invasion, was not affected significantly by the hyaluronan oligomers in two of the three invasive glioma cells tested. Another parameter that is important for invasion is production of matrix metalloproteinases, [41][42][43] whose production is regulated by the PI3K pathway 38 -40 and is stimulated by treatment with polymeric hyaluronan. 44,45 In glioma cells, hyaluronan stimulation of gelatinase B is inhibited by the tumor suppressor, PTEN, at least in part because of inactivation of focal adhesion kinase rather than the PI3K pathway.…”

Section: Discussionmentioning

confidence: 99%

Perturbation of Hyaluronan Interactions Inhibits Malignant Properties of Glioma Cells

Ward

Huang

Guo

et al. 2003

The American Journal of Pathology

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Malignant progression of gliomas is characterized by acquisition of inappropriate growth and invasive properties. In vitro, these malignant properties are reflected in, and measured by, the ability to grow in an anchorage-independent manner and to invade artificial extracellular matrices. The results of numerous studies have suggested that the extracellular and pericellular matrix polysaccharide, hyaluronan, plays an important role in these attributes of malignant cancer cells. However, with respect to glioma cells, most studies have addressed the effect of exogenously added hyaluronan rather than the function of endogenous tumor cell-associated hyaluronan. In this study we manipulate hyaluronan-glioma cell interactions by two methods. The first is administration of small hyaluronan oligosaccharides that compete for endogenous hyaluronan polymer interactions, resulting in attenuation of hyaluronan-induced signaling. The second is overexpression of soluble hyaluronanbinding proteins that act as a competitive sink for interaction with endogenous hyaluronan, again leading to attenuated signaling. We find that both treatments inhibit anchorage-independent growth, as measured by colony formation in soft agar, and invasiveness, as measured by penetration of reconstituted basement membrane matrices. Based on our findings, we conclude that endogenous hyaluronan interactions are essential for these two fundamental malignant properties of glioma cells. Malignant forms of glioblastoma rarely metastasize to distant sites but they are highly proliferative and invasive tumors that destroy normal brain structure and result in high morbidity. As with many types of cancers, up-regulation of growth factor pathways and loss of tumor suppressors have been implicated in glioma development but the mechanisms underlying progression of gliomas to malignancy are by no means established. 1 It has become increasingly apparent that cooperation between signaling pathways induced by growth factors and cytokines and those induced by cell-cell and cell-extracellular matrix interactions are central to regulation of cell behavior. Recent work has highlighted the importance of altered cell-matrix interactions in the acquisition of malignant characteristics. [2][3][4] Hyaluronan is a very large, negatively charged polysaccharide composed of repeating units of glucuronic acid and N-acetylglucosamine. It is ubiquitously associated with extracellular and pericellular matrices but is especially enriched around proliferating and migrating cells. 5 Interactions of hyaluronan with a variety of cell-surface receptors activate intracellular signaling pathways that regulate various aspects of cell behavior 6 and, in tumor cells, promote malignant characteristics. [7][8][9] Several studies have provided evidence that hyaluronan-cell interactions may play a role in glioma invasiveness. For example, addition of exogenous hyaluronan enhances glioma cell migration and invasion in vitro, and this effect is blocked by antibodies or anti-sense oligonucleotides to C...

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Section: Discussionmentioning

confidence: 99%

Perturbation of Hyaluronan Interactions Inhibits Malignant Properties of Glioma Cells

Ward

Huang

Guo

et al. 2003

The American Journal of Pathology

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“…Furthermore, expression of brevican is absent from low-invasive 9L gliosarcomas (Zhang et al, 1998) but is abundant at the invasion front of G261 glioblastomas, as is the proinvasive metalloproteinase-2 (supplemental Fig. 1e-g, available at www.jneurosci.org as supplemental material) (Koul et al, 2001).…”

Section: Characterization Of the Glioblastoma Modelmentioning

confidence: 99%

Glioblastoma-Induced Attraction of Endogenous Neural Precursor Cells Is Associated with Improved Survival

Glaß

Synowitz²,

Kronenberg³

et al. 2005

J. Neurosci.

192

172

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Neural precursor cells contribute to adult neurogenesis and to limited attempts of brain repair after injury. Here we report that in a murine experimental glioblastoma model, endogenous neural precursors migrate from the subventricular zone toward the tumor and surround it. The association of endogenous precursors with syngenic tumor grafts was observed, after injecting red fluorescent proteinlabeled G261 cells into the caudate-putamen of transgenic mice, which express green fluorescent protein under a promoter for nestin (nestin-GFP). Fourteen days after inoculation, the nestin-GFP cells surrounded the tumors in several cell layers and expressed markers of early noncommitted and committed precursors. Nestin-GFP cells were further identified by a characteristic membrane current pattern as recorded in acute brain slices. 5-Bromo-2-deoxyuridine labeling and dye tracing experiments revealed that the tumor-associated precursors originated from the subventricular zone. Moreover, in cultured explants from the subventricular zone, the neural precursors showed extensive tropism for glioblastomas. Tumor-induced endogenous precursor cell accumulation decreased with age of the recipient; this correlated with increased tumor size and shorter survival times in aged mice. Coinjection of glioblastoma cells with neural precursors improved the survival time of old mice to a level similar to that in young mice. Coculture experiments showed that neural precursors suppressed the rapid increase in tumor cell number, which is characteristic of glioblastoma, and induced glioblastoma cell apoptosis. Our results indicate that tumor cells attract endogenous precursor cells; the presence of precursor cells is antitumorigenic; and this cellular interaction decreases with aging.

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“…In vitro studies with glioma cell lines deficient in PTEN expression showed that inhibitors of PI3K (LY294002 and wortmannin), or overexpression of PTEN, reduced cell invasiveness in vitro, and this was associated with reduced activity of matrix metalloproteinases including MMP2 and MMP9 (Kubiatowski et al, 2001;Koul et al, 2001).…”

Section: Migration and Invasionmentioning

confidence: 99%

PTEN signaling in brain: neuropathology and tumorigenesis

2008

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Suppression of matrix metalloproteinase-2 gene expression and invasion in human glioma cells by MMAC/PTEN

Cited by 104 publications

References 45 publications

Perturbation of Hyaluronan Interactions Inhibits Malignant Properties of Glioma Cells

Perturbation of Hyaluronan Interactions Inhibits Malignant Properties of Glioma Cells

Glioblastoma-Induced Attraction of Endogenous Neural Precursor Cells Is Associated with Improved Survival

PTEN signaling in brain: neuropathology and tumorigenesis

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