Angiogenesis in vestibular schwannomas: Expression of extracellular matrix factors MMP‐2, MMP‐9, and TIMP‐1

Möller, Martin; Werther, Kim; Nalla, Amarnadh; Stangerup, Sven‐Eric; Thomsen, Jens; Bøg-Hansen, T.C.; Nielsen, Hans Jørgen; Cayé‐Thomasen, Per

doi:10.1002/lary.20834

Cited by 35 publications

(32 citation statements)

References 21 publications

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“…Although we do not understand what determines whether VS will grow, it is likely that inflammation has a role to play. This is supported by histological studies indicating that volume increase in VS may be due to angiogenesis with resulting new vessel formation, and correlates with the intensity of the inflammatory reaction as well as concentration of tumor‐associated macrophages . Furthermore, there is some evidence to suggest that systemic markers of inflammation are predictive of VS growth …”

Section: Introductionmentioning

confidence: 75%

“…This is supported by histological studies indicating that volume increase in VS may be due to angiogenesis with resulting new vessel formation, and correlates with the intensity of the inflammatory reaction as well as concentration of tumor-associated macrophages. [12][13][14] Furthermore, there is some evidence to suggest that systemic markers of inflammation are predictive of VS growth. 15 Aspirin exerts its anti-inflammatory action through irreversible inhibition of the cyclooxegenase pathways (COX-1 and 2), thereby reducing prostaglandins.…”

Section: Introductionmentioning

confidence: 99%

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Aspirin does not prevent growth of vestibular schwannomas: A case‐control study

et al. 2018

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Section: Introductionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Aspirin does not prevent growth of vestibular schwannomas: A case‐control study

et al. 2018

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“…204,205 We should note that MMPs may exert anti-angiogenic effects through the generation of endogenous angiogenesis inhibitors by proteolytic cleavage of certain collagen chains and plasminogen. MMP-9 mediates tamoxifen-induced increase in endostatin and thus decreases angiogenesis in hormone dependent ovarian cancer.…”

Section: Mmp Inhibitors As Investigational Tools In Biological Promentioning

confidence: 99%

Matrix Metalloproteinase Inhibitors as Investigational and Therapeutic Tools in Unrestrained Tissue Remodeling and Pathological Disorders

Liu

Khalil

2017

Progress in Molecular Biology and Translational Science

120

161

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Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes that degrade various proteins in the extracellular matrix (ECM). MMPs may also regulate the activity of membrane receptors and post-receptor signaling mechanisms, and thereby affect cell function. The MMP family includes collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs and other MMPs. Inactive proMMPs are cleaved by other MMPs or proteases into active MMPs, which interact with various protein substrates in ECM and cell surface. MMPs regulate important biological processes such as vascular remodeling and angiogenesis, and may be involved in the pathogenesis of cardiovascular disorders such as hypertension, atherosclerosis, and aneurysm. The role of MMPs is often assessed by measuring their mRNA expression, protein levels, and proteolytic activity using gel zymography. MMP inhibitors are also used to assess the role of MMPs in different biological processes and pathological conditions. MMP activity is regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and the MMP/TIMP balance could determine the net MMP activity, ECM turnover, and tissue remodeling. Also, several synthetic MMP inhibitors have been developed. Synthetic MMP inhibitors include a large number of zinc binding globulins (ZBGs), in addition to non-ZBGs and mechanism-based inhibitors. MMP inhibitors have been proposed as potential tools in the management of osteoarthritis, cancer, and cardiovascular disorders. However, most MMP inhibitors have broad-spectrum actions on multiple MMPs and could cause undesirable musculoskeletal side effects. Currently, doxycycline is the only MMP inhibitor approved by the Food and Drug Administration. New generation biological and synthetic MMP inhibitors may show greater MMP specificity and fewer side-effects, and could be useful in targeting specific MMPs, reducing unrestrained tissue remodeling, and the management of MMP-related pathological disorders.

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“…Vascularization and new blood vessel development are an important aspect of solid tumor growth in general [3] and have also been involved in the specific case of VS growth [4,5,6,7]. Among the numerous proangiogenic growth factors, the vascular endothelial growth factor (VEGF) is considered to be a major regulator of angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

The VEGF/VEGF-R Axis in Sporadic Vestibular Schwannomas Correlates with Irradiation and Disease Recurrence

Koutsimpelas

Bjelopavlovic²,

Yetis³

et al. 2012

ORL

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Background/Aims: The molecular mechanisms downstream of mutated neurofibromatosis type 2 (NF2) gene resulting in the growth and development of vestibular schwannoma (VS) are controversial. Several lines of evidence suggest the involvement of the vascular endothelial growth factor (VEGF) pathway in VS development. Given that recent studies of VEGF blockade in patients with NF2-associated VS showed positive effects on VS growth control, we initiated this comprehensive study of the VEGF pathway in sporadic VS. Methods: A tissue microarray analysis of 182 sporadic VS was conducted. The expression of VEGF and its receptors as well as the proliferative activity of the tumors were quantified. The expression data were correlated to tumor volumes and diameters as well as to tumor recurrence and previous irradiation. Results: All studied tumors expressed VEGF and its receptors. Proliferative activity was related to the growth characteristics of the tumors. Moreover, we found significantly higher VEGF levels in recurrent tumors(p = 0.0387) and in preoperatively irradiated tumors (p = 0.0213). Conclusion: Our data suggest a relevant role of the VEGF pathway in VS growth and therapy outcome. Therefore, targeting this pathway using antiangiogenic compounds might be beneficial for patients with sporadic VS, especially those with recurrent or irradiated tumors.

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Angiogenesis in vestibular schwannomas: Expression of extracellular matrix factors MMP‐2, MMP‐9, and TIMP‐1

Cited by 35 publications

References 21 publications

Aspirin does not prevent growth of vestibular schwannomas: A case‐control study

Aspirin does not prevent growth of vestibular schwannomas: A case‐control study

Matrix Metalloproteinase Inhibitors as Investigational and Therapeutic Tools in Unrestrained Tissue Remodeling and Pathological Disorders

The VEGF/VEGF-R Axis in Sporadic Vestibular Schwannomas Correlates with Irradiation and Disease Recurrence

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