An immunohistochemical study of extracellular matrix proteins laminin, fibronectin and type IV collagen in paediatric glioblastoma multiforme

Caffo, Maria; Germanò, A.; Caruso, Gerardo; Meli, Francesco; Galatioto, S; Sciacca, Miriam; Tomasello, Francesco

doi:10.1007/s00701-004-0344-y

Cited by 22 publications

(16 citation statements)

References 20 publications

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“…Several studies addressed the relation between fibronectin and tumors, including breast cancer, melanoma (30,31), and gliomas. Overexpression of fibronectin in glioblastoma as detected by immunohistochemistry was reported previously (32). The expression of fibronectin by glioma blood vessels suggests that this protein plays a role in the development of glioma vasculature (33).…”

Section: Discussionmentioning

confidence: 52%

Identification of Glioma Neovascularization-related Proteins by Using MALDI-FTMS and Nano-LC Fractionation to Microdissected Tumor Vessels

Mustafa¹,

Burgers

Dekker

et al. 2007

Molecular & Cellular Proteomics

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The identification of angiogenesis-related proteins is important for the development of new antiangiogenic therapies, and such proteins are potential new biomarkers for gliomas. The aim of this study was to identify proteins that are exclusively present in glioma neovasculature and not in the vasculature of normal brain. We combined advanced proteomics techniques to compare the expression profiles of microdissected blood vessels from glioma with blood vessels of normal control brain samples. We measured the enzymatic generated peptide profiles from these microdissected samples by MALDI-FTMS. Subsequently, the samples were fractionated by nano-LC prior to MALDI-TOF/TOF. This combined approach enabled us to identify four proteins that appeared to be exclusively expressed in the glioma blood vessels. Two of these proteins, fibronectin and colligin 2, were validated on tissue sections using specific antibodies. We found that both proteins are present in active angiogenesis in glioma, other neoplasms, and reactive conditions in which neoangiogenesis takes place. This work proves that gel-free mass spectrometric techniques can be used on relatively

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Section: Discussionmentioning

confidence: 52%

Identification of Glioma Neovascularization-related Proteins by Using MALDI-FTMS and Nano-LC Fractionation to Microdissected Tumor Vessels

Mustafa¹,

Burgers

Dekker

et al. 2007

Molecular & Cellular Proteomics

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“…However, the nature of potential substrates and interactions of LOX with these substrates in the CNS is not known. In addition to collagen type I [11] and type IV [1], invasive astrocytes are known to aberrantly secrete a large amount of tropoelastin that becomes degraded without assembly [12]. Invasive astrocyte‐derived elastin, in addition to being a potential adhesive media, may provide unusually high local substrate concentration for LOX, resulting in increased generation of hydrogen peroxide, subsequent hydrogen peroxide‐mediated signalling and enhanced cell migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

“…Components of the extracellular matrix (ECM) play a critical role during normal and pathological conditions in the central nervous system (CNS), including the development and invasion of primary brain tumours [1,2]. The invasive phenotype of astrocytes is a hallmark of tumour progression, but the molecular mechanisms that control the invasive cell behaviour, the role of the locally permissive ECM, and cell–ECM signalling in this matrix environment are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Active lysyl oxidase (LOX) correlates with focal adhesion kinase (FAK)/paxillin activation and migration in invasive astrocytes

Laczkó

Szauter

Jansen

et al. 2007

Neuropathology Appl Neurobio

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The extracellular matrix (ECM) plays a critical role during the development and invasion of primary brain tumours. However, the function of ECM components and signalling between a permissive ECM and invasive astrocytes is not fully understood. We have recently reported the ECM enzyme, lysyl oxidase (LOX), in the central nervous system and observed up-regulation of LOX in anaplastic astrocytoma cells. While the catalytic function of LOX is essential for cross-linking of ECM proteins, we also reported that LOX induced invasive and metastatic properties in breast tumour epithelial cells through hydrogen peroxide-mediated FAK/Src activation. In this study, we tested the hypothesis that active LOX is expressed in anaplastic astrocytes and promotes FAK activation and invasive/migratory behaviour. Results demonstrate that increased expression and activity of LOX positively correlated with invasive phenotype of malignant astrocytoma cell lines. Immunohistochemistry detected increased LOX within tumour cells and ECM in grade I-IV astrocytic neoplasm compared with normal brain and coincidence of increased LOX with the loss of glial fibrillary acidic protein in higher-grade tumours. Increased active LOX in invasive astrocytes was accompanied by phosphorylation of FAK[Tyr576] and paxillin[Tyr118]; furthermore, both FAK and paxillin tyrosine phosphorylation were diminished by beta-aminopropionitrile inhibition of LOX activity and depletion of H(2)O(2) via catalase treatment. Additionally, we provide evidence that in astrocytes, LOX is likely processed by bone morphogenic protein-1 and LOX activity might be further stimulated by the expression of fibronectin in these cells. These results demonstrate an important LOX-mediated mechanism that promotes migratory/invasive behaviour of malignant astrocytes.

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“…Glioblastomas are defined by an accumulation of several large ECM-components, i.e. collagens I, IV, VI, and fibronectin, laminin, versican, decorin, and tenascin-C [17,18]. It has been demonstrated that increasing concentrations of collagen I correlate positively with tumour invasiveness, but negatively with tumour growth.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Collagen XVI Expression Reduces Glioma Cell Invasiveness

Bauer¹,

Ratzinger²,

Wales³

et al. 2011

Cell Physiol Biochem

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Glioblastomas are characterized by an intense local invasiveness that limits surgical resection. One mechanism by which glioma cells enforce their migration into brain tissue is reorganization of tumour associated extracellular matrix (ECM). Collagen XVI is a minor component of connective tissues. However, in glioblastoma tissue it is dramatically upregulated compared to the ECM of normal cortex. The aim of this study is to delineate tumour cell invasion and underlying mechanisms involving collagen XVI by using a siRNA mediated collagen XVI knockdown model in U87MG human glioblastoma cells. Knockdown of collagen XVI resulted in decreased invasiveness in Boyden chamber assays, and in a reduction of focal adhesion contact numbers per cell. Gene expression was upregulated for protocadherin 18 and downregulated for kindlin-1 and -2. Proliferation was not affected while flow cytometric analysis demonstrated reduced β1-integrin activation in collagen XVI knockdown cells. We suggest that in glioblastoma tissue collagen XVI may impair the cell-cell interaction in favour of enhancement of invasion. The modification of the β1-integrin activation pattern through collagen XVI might be a molecular mechanism to further augment the invasive phenotype of glioma cells. Elucidating the underlying mechanisms of glioma cell invasion promoted by collagen XVI may provide novel cancer therapeutic approaches in neurooncology.

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An immunohistochemical study of extracellular matrix proteins laminin, fibronectin and type IV collagen in paediatric glioblastoma multiforme

Cited by 22 publications

References 20 publications

Identification of Glioma Neovascularization-related Proteins by Using MALDI-FTMS and Nano-LC Fractionation to Microdissected Tumor Vessels

Identification of Glioma Neovascularization-related Proteins by Using MALDI-FTMS and Nano-LC Fractionation to Microdissected Tumor Vessels

Active lysyl oxidase (LOX) correlates with focal adhesion kinase (FAK)/paxillin activation and migration in invasive astrocytes

Inhibition of Collagen XVI Expression Reduces Glioma Cell Invasiveness

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