X-rays modulate extracellular matrixin vivo

Giannopoulou, Efstathia; Katsoris, Panagiotis; Hatziapostolou, Maria; Kardamakis, D.; Kotsaki, Elena; Polytarchou, Christos; Parthymou, Anastasia; Papaioannou, Stamatis; Papadimitriou, Evangelia

doi:10.1002/ijc.1535

Cited by 54 publications

(12 citation statements)

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“…Previous studies have demonstrated FN expression was significantly altered at both the transcript and protein levels in response to irradiation (20,38). In this study we have shown a significant time-and dose-dependent decrease in FN protein levels when cells were treated with UV irradiation.…”

Section: Discussionsupporting

confidence: 64%

Constitutive and UV-induced Fibronectin Degradation Is a Ubiquitination-dependent Process Controlled by β-TrCP

Ray

Osmundson

Kiyokawa

2006

Journal of Biological Chemistry

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Loss of fibronectin (FN) assembly in the extracellular matrix has long been recognized as a feature of cellular transformation. However, such assembly is regulated not only by FN synthesis but also by its post-translational modifications. The mechanism controlling FN protein stability has remained unclear so far. Recently it was demonstrated that FN matrix turnover occurs intracellularly at the lysosome following caveolin-1-dependent endocytosis. Although FN was reported to undergo ubiquitindependent degradation, the ubiquitin ligase responsible for FN ubiquitination is unknown. In this study, we have identified ␤-TrCP as the ubiquitin ligase for lysosomal degradation of FN. We found two conserved ␤-TrCP recognition motif (DSGVVYS and DSGSIVVS) in the primary amino acid sequence of human, mouse, and rat FN. Down-regulation of either ␤-TrCP1 or ␤-TrCP2 by small interference (siRNA) caused significant accumulation of FN. Immunolocalization studies showed intracellular accumulation of FN in ␤-TrCP siRNA-treated cells without showing much alteration in its matrix association. We also observed that exposure of cells to UV irradiation effectively down-regulated FN following increased ubiquitination, which was significantly inhibited either by lysosomal inhibitor or by siRNA-mediated down-regulation of ␤-TrCP. Taken together, constitutive FN degradation, as well as UV-induced degradation, is ubiquitination dependent and controlled by ␤-TrCP. Fibronectin (FN),2 a matrix glycoprotein, plays important roles in cell adhesion, migration, growth, and differentiation (1). The functional FN consists of two 250-kDa subunits linked covalently near their C termini by a pair of disulfide bonds. There are two different forms of fibronectins: plasma "cold insoluble globulin" and tissue FNs. Both forms originate from the same gene by alternative splicing in three different regions (EIIIA, EIIIB, and IIICS), giving rise to ϳ20 isoforms (2). FN generally interacts with integrins, a major component of the extracellular matrix (ECM), and thereby facilitates bilateral exchange of information between cells and the matrix environment (3). It has been known for decades that malignant transformation modifies such cell-matrix interactions (4), and perturbed FN matrix assembly has been recognized as a hallmark of transformed cells (5, 6). During transformation cells lose their surface FN, which has so far been attributed either to transcriptional down-regulation or to proteolytic degradation (7,8). However, it is obscure how post-translational modifications control the metabolism of FN. It is necessary to study FN protein stability because significant up-regulation of FN protein has been detected in metastatic breast cancer tissues, without significant increase in the transcript levels (9).It has been well established that ubiquitination plays an important role in proteasomal degradation of proteins. Recent findings also emphasize the role of ubiquitination in endocytosis of plasma membrane-associated proteins followed by their sorting and lyso...

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Section: Discussionsupporting

confidence: 64%

Constitutive and UV-induced Fibronectin Degradation Is a Ubiquitination-dependent Process Controlled by β-TrCP

Ray

Osmundson

Kiyokawa

2006

Journal of Biological Chemistry

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“…Not surprisingly X rays have been shown to decrease the number of blood vessels, most probably due to vascular targeting within the first hours after irradiation [152]. However, it appears that X-rays promote multiple effects in the CAM: (i) induce early apoptosis of CAM cells, a property that can be exploited to screen radioprotective compounds [153], (ii) modulate the synthesis and deposition of extracellular matrix proteins involved in regulating angiogenesis and (iii) affect angiogenesis induced by tumor cells implanted onto the CAM [154]. More recently, the CAM/embryos has been used to test the activity of radiosensitizers.…”

Section: Cam As a Screening Platformmentioning

confidence: 99%

The chicken chorioallantoic membrane model in biology, medicine and bioengineering

2014

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The chicken chorioallantoic membrane (CAM) is a simple, highly vascularized extraembryonic membrane, which performs multiple functions during embryonic development, including but not restricted to gas exchange. Over the last two decades, interest in the CAM as a robust experimental platform to study blood vessels has been shared by specialists working in bioengineering, development, morphology, biochemistry, transplant biology, cancer research and drug development. The tissue composition and accessibility of the CAM for experimental manipulation, makes it an attractive preclinical in vivo model for drug screening and / or for studies of vascular growth. In this article we provide a detailed review of the use of the CAM to study vascular biology and response of blood vessels to a variety of agonists. We also present distinct cultivation protocols discussing their advantages and limitations and provide a summarized update on the use of the CAM in vascular imaging, drug delivery, pharmacokinetics and toxicology.

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“…Increasing cellular movement in malignant gliomas would undermine the therapeutical intent and possibly impose a greater risk of deep locoregional tumor infiltration and metastasization in vivo onto the patients than even without therapy. Furthermore, photon irradiation is kown to modulate the expression of extracellular matrix proteins and thus alter the motility-determining environment of malignant gliomas [9]. …”

Section: Introductionmentioning

confidence: 99%

Targeting ανβ3 and ανβ5 inhibits photon-induced hypermigration of malignant glioma cells

et al. 2011

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BackgroundSublethal photon irradiation was recently suspected to increase tumor cell motility and promote locoregional recurrence of disease. This study was set up to describe mechanisms underlying increased glioma cell migration through photon irradiation and to analyse the modifiability of photon-altered glioma cell motility by integrin inhibition.MethodsEight μm pore size membranes were coated with vitronectin (VN), collagen I and collagen IV. U87 and Ln229 glioma cells were analysed in migration experiments with and without radiotherapy (RT), serum stimulation and addition of monoclonal antibodies directed to human integrins ανβ3 and ανβ5. Quantitative FACS analysis of integrins was performed in U87 and Ln229 glioma cells following RT. Statistical analysis was performed using Student's t-test.ResultsGlioma cell migration is serum-dependent and can be increased by photon RT which leads to enhanced expression of Vn receptor integrins. Blocking of either ανβ3 or ανβ5 integrins by antibodies inhibits Vn-based migration of both untreated and photon-irradiated glioma cells.ConclusionsPeripheral glioma cells are at risk of attraction into the adjacent healthy brain by serum components leaking through the blood brain barrier (BBB). Radiation therapy is associated with upregulation of Vn receptor integrins and enhanced glioma cell migration at sublethal doses. This effect can be inhibited by specific integrin blockade. Future therapeutical benefit may be derived from pharmacological integrin inhibition in combination with photon irradiation.

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X-rays modulate extracellular matrixin vivo

Cited by 54 publications

References 50 publications

Constitutive and UV-induced Fibronectin Degradation Is a Ubiquitination-dependent Process Controlled by β-TrCP

Constitutive and UV-induced Fibronectin Degradation Is a Ubiquitination-dependent Process Controlled by β-TrCP

The chicken chorioallantoic membrane model in biology, medicine and bioengineering

Targeting ανβ3 and ανβ5 inhibits photon-induced hypermigration of malignant glioma cells

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