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Jäälinoja, Juha; Herva, Riitta; Korpela, Merja; Höyhtyä, Matti; Turpeenniemi‐Hujanen, Taina

doi:10.1023/a:1006421112839

Cited by 70 publications

(14 citation statements)

References 36 publications

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“…Further, these model results suggest exploration of invasion-specific markers (e.g. MMP-2 (33), vimentin (34)) may enhance the prognostic accuracy of the current grading scheme. Admittedly, assessing invasion from fixed histological sections of dead tissue is a true challenge.…”

Section: Discussionmentioning

confidence: 93%

Quantifying the Role of Angiogenesis in Malignant Progression of Gliomas: In Silico Modeling Integrates Imaging and Histology

et al. 2011

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Gliomas are uniformly fatal forms of primary brain neoplasms that vary from low-grade to high-grade (glioblastoma). While low-grade gliomas are weakly angiogenic, glioblastomas are among the most angiogenic of tumors. Thus, interactions between glioma cells and their tissue microenvironment may play an important role in aggressive tumor formation and progression. To quantitatively explore how tumor cells interact with their tissue microenvironment, we incorporated the interactions of normoxic glioma cells, hypoxic glioma cells, vascular endothelial cells, diffusible angiogenic factors, and necrosis formation into a first-generation, biologically-based mathematical model for glioma growth and invasion. Model simulations quantitatively described the spectrum of in vivo dynamics of gliomas visualized with medical imaging. Further, we investigated how proliferation and dispersal of glioma cells combine to induce increasing degrees of cellularity, mitoses, hypoxia-induced neo-angiogenesis and necrosis, features that characterize increasing degrees of “malignancy”, and we found that changes in the net rates of proliferation ({lower case rho}) and invasion (D) are not always necessary for malignant progression. Thus, although other factors, including the accumulation of genetic mutations, can change cellular phenotype (e.g. proliferation and invasion rates), this study suggests that these are not required for malignant progression. Simulated results are placed in the context of the current clinical World Health Organization grading scheme for studying specific patient examples. This study suggests that through the application of the proposed model for tumor-microenvironment interactions, predictable patterns of dynamic changes in glioma histology distinct from changes in cellular phenotype (e.g. proliferation and invasion rates) may be identified, thus providing a powerful clinical tool.

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Section: Discussionmentioning

confidence: 93%

Quantifying the Role of Angiogenesis in Malignant Progression of Gliomas: In Silico Modeling Integrates Imaging and Histology

et al. 2011

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“…In one study of brain metastasis, MMP-2 was identified in all metastases regardless of site of origin. Moreover, MMP-2 activity correlated inversely with survival [55]. In a murine tumor model, the incidence of brain metastasis was reduced by 75% when compared to the wild type following the use of tissue inhibitor of metalloprotease1 (TIMP-1), which suggests that inhibitors of MMPs suppress BrMs [56].…”

Section: The Metastatic Processmentioning

confidence: 99%

The Molecular Biology of Brain Metastasis

Rahmathulla

Toms

Weil

2012

Journal of Oncology

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Metastasis to the central nervous system (CNS) remains a major cause of morbidity and mortality in patients with systemic cancers. Various crucial interactions between the brain environment and tumor cells take place during the development of the cancer at its new location. The rapid expansion in molecular biology and genetics has advanced our knowledge of the underlying mechanisms involved, from invasion to final colonization of new organ tissues. Understanding the various events occurring at each stage should enable targeted drug delivery and individualized treatments for patients, with better outcomes and fewer side effects. This paper summarizes the principal molecular and genetic mechanisms that underlie the development of brain metastasis (BrM).

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“…The biological role and functional contribution of MMPs is complex and their role in meningiomas is far from established. Previous studies have focused on establishing the role of MMP2 in meningiomas, in particular as it relates to tumor recurrence, brain invasion, and peritumoral edema, and the data is conflicting [10, 19, 21, 23, 24, 26, 28–31, 48]. Though some studies found higher MMP2 expression levels in recurrent meningiomas [28, 48], others have found no association between meningioma grade and MMP2 levels [29].…”

Section: Discussionmentioning

confidence: 99%

“…Studies focused on the predictive potential of MMP2 on meningioma peritumoral edema have been contradictory, with Paek et al [30] suggesting a positive association, whereas Panagopolous et al [31] noted no such association. Yet Jaalinoja et al [19] found no MMP-2 expression in benign meningiomas altogether.…”

Section: Discussionmentioning

confidence: 99%

Proteins involved in regulating bone invasion in skull base meningiomas

et al. 2012

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BackgroundBone invasive skull base meningiomas are a subset of meningiomas that present a unique clinical challenge due to brain and neural structure involvement and limitations in complete surgical resection, resulting in higher recurrence and need for repeat surgery. To date, the pathogenesis of meningioma bone invasion has not been investigated. We investigated immunoexpression of proteins implicated in bone invasion in other tumor types to establish their involvement in meningioma bone invasion.MethodsRetrospective review of our database identified bone invasive meningiomas operated on at our institution over the past 20 years. Using high-throughput tissue microarray (TMA), we established the expression profile of osteopontin (OPN), matrix metalloproteinase-2 (MMP2), and integrin beta-1 (ITGB1). Differential expression in tumor cell and vasculature was evaluated and comparisons were made between meningioma anatomical locations.ResultsMMP2, OPN, and ITGB1 immunoreactivity was cytoplasmic in tumor and/or endothelial cells. Noninvasive transbasal meningiomas exhibited higher vascular endothelial cell MMP2 immunoexpression compared to invasive meningiomas. We found higher expression levels of OPN and ITGB1 in bone invasive transbasal compared to noninvasive meningiomas. Strong vascular ITGB1 expression extending from the endothelium through the media and into the adventitia was found in a subset of meningiomas.ConclusionsWe have demonstrated that key proteins are differentially expressed in bone invasive meningiomas and that the anatomical location of bone invasion is a key determinant of expression pattern of MMP1, OPN, and ITGB1. This data provides initial insights into the pathophysiology of bone invasion in meningiomas and identifies factors that can be pursued as potential therapeutic targets.

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Abstract: Our data suggest that MMP-2 is associated with histological malignancy and poor survival in brain tumors.

Cited by 70 publications

References 36 publications

Quantifying the Role of Angiogenesis in Malignant Progression of Gliomas: In Silico Modeling Integrates Imaging and Histology

Quantifying the Role of Angiogenesis in Malignant Progression of Gliomas: In Silico Modeling Integrates Imaging and Histology

The Molecular Biology of Brain Metastasis

Proteins involved in regulating bone invasion in skull base meningiomas

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