Expression of extracellular matrix components in a highly infiltrative in vivo glioma model

Mahesparan, Rupavathana; Read, Tracy Ann; Lund‐Johansen, Morten; Skaftnesmo, Kai Ove; Bjerkvig, Rolf; Engebraaten, Olav

doi:10.1007/s00401-002-0610-0

Cited by 162 publications

(101 citation statements)

References 23 publications

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“…In the center area of U87ΔEGFR tumors following bevacizumab treatment and combination therapy of bevacizumab and cilengitide, ECMs were thickened remarkably at perivascular space with respectively different characteristics. Fibronectin, vitronectin, laminin, tenascin, and different types of collagen promote invasion of glioma [29], [30]; in contrast, glycosylated chondroitin sulfate proteoglycans consisting ECMs inhibit invasion in glioma [31]. These different mechanisms might be necessary for the regulation of tumor angiogenesis and invasion; however, the detailed mechanisms have not been elucidated and they need to be clarified in the future.…”

Section: Discussionmentioning

confidence: 99%

Integrin Inhibitor Suppresses Bevacizumab-Induced Glioma Invasion

Ishida

Onishi

Kurozumi

et al. 2014

Translational Oncology

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Glioblastoma is known to secrete high levels of vascular endothelial growth factor (VEGF), and clinical studies with bevacizumab, a monoclonal antibody to VEGF, have demonstrated convincing therapeutic benefits in glioblastoma patients. However, its induction of invasive proliferation has also been reported. We examined the effects of treatment with cilengitide, an integrin inhibitor, on bevacizumab-induced invasive changes in glioma. U87ΔEGFR cells were stereotactically injected into the brain of nude mice or rats. Five days after tumor implantation, cilengitide and bevacizumab were administered intraperitoneally three times a week. At 18 days after tumor implantation, the brains were removed and observed histopathologically. Next, the bevacizumab and cilengitide combination group was compared to the bevacizumab monotherapy group using microarray analysis. Bevacizumab treatment led to increased cell invasion in spite of decreased angiogenesis. When the rats were treated with a combination of bevacizumab and cilengitide, the depth of tumor invasion was significantly less than with only bevacizumab. Pathway analysis demonstrated the inhibition of invasion-associated genes such as the integrin-mediated cell adhesion pathway in the combination group. This study showed that the combination of bevacizumab with cilengitide exerted its anti-invasive effect. The elucidation of this mechanism might contribute to the treatment of bevacizumab-refractory glioma.

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Section: Discussionmentioning

confidence: 99%

Integrin Inhibitor Suppresses Bevacizumab-Induced Glioma Invasion

Ishida

Onishi

Kurozumi

et al. 2014

Translational Oncology

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“…These molecules have been found repeatedly to enhance cell survival, proliferation, and migration in vitro and in vivo [34–38]. Furthermore, the proteoglycan tenascin-C is produced by tumor-associated endothelial cells and its presence correlates with angiognenesis and the progression from grade II to grade III glioma [39,40]. …”

Section: Role Of Microenvironment In Gbm Progressionmentioning

confidence: 99%

Engineering strategies to mimic the glioblastoma microenvironment

Rape

Ananthanarayanan

Kumar

2014

Advanced Drug Delivery Reviews

129

114

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Glioblastoma multiforme (GBM) is the most common and deadly brain tumor, with a mean survival time of only 21 months. Despite the dramatic improvements in our understanding of GBM fueled by recent revolutions in molecular and systems biology, treatment advances for GBM have progressed inadequately slowly, which is due in part to the wide cellular and molecular heterogeneity both across tumors and within a single tumor. Thus, there is increasing clinical interest in targeting cell-extrinsic factors as way of slowing or halting the progression of GBM. These cell-extrinsic factors, collectively termed the microenvironment, include the extracellular matrix, blood vessels, stromal cells that surround tumor cells, and all associated soluble and scaffold-bound signals. In this review, we will first describe the regulation of GBM tumors by these microenvironmental factors. Next, we will discuss the various in vitro approaches that have been exploited to recapitulate and model the GBM tumor microenvironment in vitro. We conclude by identifying future challenges and opportunities in this field, including the development of microenvironmental platforms amenable to high-throughput discovery and screening. We anticipate that these ongoing efforts will prove to be valuable both as enabling tools for accelerating our understanding of microenvironmental regulation in GBM and as foundations for next-generation molecular screening platforms that may serve as a conceptual bridge between traditional reductionist systems and animal or clinical studies.

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“…α 2 β 1, α 3 β 1 , and α 5 β 1 integrins are overexpressed in multidrug-resistant glioma cells and are responsible for their increased adhesive and invasive capacities (Hikawa et al, 2000). The laminin-5 receptor α 3 β 1 integrin is mainly expressed in areas of tumor cell invasion and support glioma cell migration and invasion (Tysnes et al, 1996; Mahesparan et al, 2003; Kawataki et al, 2007). α v β 3 integrins promote migration and adhesion in various glioma cells (Gladson and Cheresh, 1991; Friedlander et al, 1996) and inhibition of α v β 3 integrin with neutralizing antibody inhibited migration and invasion selectively in cell lines that contained a high level of integrin expression (Wild-Bode et al, 2001).…”

Section: Integrins In Gliomamentioning

confidence: 99%

Integrins and p53 pathways in glioblastoma resistance to temozolomide

Martin¹,

Janoušková²,

Dontenwill³

2012

Front. Oncol.

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Glioblastoma is the most common malignant primary brain tumor. Surgical resection, postoperative radiotherapy plus concomitant and adjuvant chemotherapy with temozolomide (TMZ) is the standard of care for newly diagnosed glioblastoma. In the past decade, efforts have been made to decipher genomic and core pathway alterations to identify clinically relevant glioblastoma subtypes. Based on these studies and more academic explorations, new potential therapeutic targets were found and several targeting agents were developed. Such molecules should hopefully overcome the resistance of glioblastoma to the current therapy. One of the hallmarks of glioblastoma subtypes was the enrichment of extracellular matrix/invasion-related genes. Integrins, which are cell adhesion molecules important in glioma cell migration/invasion and angiogenesis were one of those genes. Integrins seem to be pertinent therapeutic targets and antagonists recently reached the clinic. Although the p53 pathway appears often altered in glioblastoma, conflicting results can be found in the literature about the clinically relevant impact of the p53 status in the resistance to TMZ. Here, we will summarize the current knowledge on (1) integrin expression, (2) p53 status, and (3) relationship between integrins and p53 to discuss their potential impact on the resistance of glioblastoma to temozolomide.

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Expression of extracellular matrix components in a highly infiltrative in vivo glioma model

Cited by 162 publications

References 23 publications

Integrin Inhibitor Suppresses Bevacizumab-Induced Glioma Invasion

Integrin Inhibitor Suppresses Bevacizumab-Induced Glioma Invasion

Engineering strategies to mimic the glioblastoma microenvironment

Integrins and p53 pathways in glioblastoma resistance to temozolomide

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