Endothelial cell marker PAL-E reactivity in brain tumor, developing brain, and brain disease

Leenstra, Sieger; Troost, Dirk; Das, PK; Claessen, Nike; Ae, Becker; Da, Bosch

doi:10.1002/1097-0142(19931115)72:10<3061::aid-cncr2820721031>3.0.co;2-6

Cited by 31 publications

(26 citation statements)

References 17 publications

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“…One such marker, the PAL-E antigen, was discovered almost 20 years ago to be expressed by endothelial cells lining blood capillaries and venules but not by lymphatic or arterial endothelium (25). Since its discovery, PAL-E antibody has been used extensively to distinguish blood from lymphatic endothelial cells, and elevated levels of PAL-E antigen have been associated with specific vascular beds, including high endothelial venules, tumor blood vessels, and blood vessels at sites of inflammation (12,13,22,23,25). Despite its extensive characterization and association with human disease states, however, the protein recognized by the PAL-E antibody has remained unknown.…”

Section: Vol 24 2004 Pal-e Identifies Vimentin From Blood Endothelimentioning

confidence: 99%

“…Identified almost 20 years ago, the PAL-E antibody was generated by the injection of human melanoma lymph node metastases into mice (25). PAL-E antibody recognizes a protein expressed exclusively by the endothelial cells that line blood capillaries and small veins, with the notable exception of those in the brain (12,23,25). Tumor blood vessels and the high endothelial venules in lymph nodes are particularly PAL-E reactive (13,25).…”

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confidence: 99%

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The Endothelial Cell-Specific Antibody PAL-E Identifies a Secreted Form of Vimentin in the Blood Vasculature

deWaal²,

Mor‐Vaknin

et al. 2004

Molecular and Cellular Biology

104

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During mammalian vascular development, endothelial cells form a complex array of vessels that differ markedly in structure and function, but the molecular basis for this vascular complexity is poorly understood. Recent insights into endothelial diversity have come from the identification of molecular markers expressed on distinct endothelial cell populations. One such marker, the PAL-E antibody, has been used for almost 20 years to distinguish blood and lymphatic vessels, but the identity of the protein recognized by PAL-E has been unknown. In the present study we have used protein purification and tandem mass spectrometry analysis of tryptic peptides to identify the PAL-E antigen as a secreted form of vimentin. Vimentin has been well characterized as an intracellular intermediate filament protein expressed broadly in mesenchymal cells. In contrast, PAL-E-reactive vimentin is secreted extracellularly, its synthesis is restricted to a distinct population of blood endothelial cells and activated macrophages, and PAL-E-reactive vimentin is found in circulating human blood. PAL-E-reactive vimentin does not arise from an endothelial cell-specific mRNA transcript but is the product of cell-specific posttranslational modification. The PAL-E antibody therefore defines secretion of vimentin as a molecular distinction among endothelial cells and exposes a novel, extracellular role for vimentin in the blood vasculature.

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Section: Vol 24 2004 Pal-e Identifies Vimentin From Blood Endothelimentioning

confidence: 99%

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confidence: 99%

The Endothelial Cell-Specific Antibody PAL-E Identifies a Secreted Form of Vimentin in the Blood Vasculature

deWaal²,

Mor‐Vaknin

et al. 2004

Molecular and Cellular Biology

104

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“…Commonly used methods of glioblastoma radioimmunolocalization, such as targeting with antibodies to fibronectin (Moosmayer et al 2006), tenascin (Akabani et al 2005), growth factor receptors (Brady et al 1992;Trojan et al 2007), endothelial antigens (Carson-Walter et al 2005;Leenstra et al 1993;Soria et al 2004), are rather limited. Low tumor specificity of these antibodies, which leads to significant irradiation of other tissues, restricts clinical applications of these methods and makes the search for new targets highly important.…”

Section: Introductionmentioning

confidence: 99%

Targeted Transport of 125I-Labeled Antibody to GFAP and AMVB1 in an Experimental Rat Model of C6 Glioma

Chekhonin

Baklaushev

Yusubalieva

et al. 2008

J Neuroimmune Pharmacol

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Glioblastoma is the most common high-grade glioma characterized by strikingly poor therapeutic outcome with survival time of about a year. This makes a search for new therapeutic approaches to glioblastoma treatment an area of great clinical importance. The present study aims to explore the potential of targeted delivery of 125I-radiolabeled antibodies, specific to glial fibrillary acidic protein (GFAP) and AMVB1 (antigen of abluminal membrane of endotheliocytes predominantly expressed in glioblastoma microvessels) as a strategy for in vivo tumor targeting. Rat C6 glioma model was used to test this hypothesis. Tumor bearing animals, injected with radiolabeled monoclonal antibodies to GFAP or AMVB1, were compared to control group, which received nonspecific mouse IgG. Radioactivity of blood, brain hemispheres, and some other tissues was measured 6, 24, 48, 72, and 96 h posttreatment. Our results demonstrate accumulation of both types of antibodies in tumors. Concentrations of both antibodies were significantly increased in tumor-bearing hemisphere compared to intact hemisphere. Antibodies to GFAP specifically accumulated in brain and bound tumor tissue with the high affinity. In contrast, increased accumulation of anti-AMVB1 antibody was detected in antigen-expressing organs, such as spleen and kidney. Based on results presented, we propose that the monoclonal antibodies to GFAP can be used as vectors for the delivery of diagnostic and pharmacological agents to high-grade gliomas. Development of this strategy would open new clinical perspectives for glioblastoma diagnostics and therapy.

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“…However, its expression is induced in brain tumors simultaneously with the loss of the blood-brain barrier. 5 Expression of PAL-E antigen is also increased on endocardium of rejected human cardiac allografts. 6 Plasmalemmal vesicle 1 (PV-1) has been described as a glycoprotein associated to plasmalemmal vesicles (caveolae).…”

Section: Introductionmentioning

confidence: 99%

Molecular identification of PAL-E, a widely used endothelial-cell marker

Niemelä

Elima

Henttinen

et al. 2005

Blood

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The pathologische anatomie Leidenendothelium (PAL-E) antibody has been used for almost 20 years as a specific marker for vascular endothelial cells. Due to the fact that this antibody works only in very limited applications, the molecular identity of PAL-E has remained unknown. IntroductionSeveral antigens including factor VIII, CD31, CD36, ulex europaeus lectin, and pathologische anatomie Leiden-endothelium (PAL-E) have been used as endothelial cell markers in a vast number of publications. However, none of these markers is perfect, because they either do not stain all types of endothelia or are not specific for vasculature. PAL-E has been considered a good marker because it discriminates blood vessel endothelium from lymphatic endothelium and does not stain other cell types. 1-3 Despite the relatively wide use of PAL-E as an endothelial marker, its molecular identity has remained an enigma, most likely due to the limited applicability of the antibody against the PAL-E molecule. However, a recent report suggests that the PAL-E antigen is a secreted form of vimentin. 4 The molecule defined by PAL-E is widely expressed on vasculature in different organs except in the brain. However, its expression is induced in brain tumors simultaneously with the loss of the blood-brain barrier. 5 Expression of PAL-E antigen is also increased on endocardium of rejected human cardiac allografts. 6 Plasmalemmal vesicle 1 (PV-1) has been described as a glycoprotein associated to plasmalemmal vesicles (caveolae). It is a 60-type II transmembrane protein that tends to form homodimers. Its cellular localization in the rat has been carefully analyzed both at light and electron microscopic levels. 7,8 However, the function of PV-1 has remained unknown. Expression of rat PV-1 is developmentally regulated in testis and it binds heparin. 9 The protein sequences of rat and mouse PV-1 have phosphorylation site(s) for casein kinase II, but this site is lacking in the human sequence. 10 The corresponding human sequence does not bear significant homology to any other known proteins, and, therefore, the sequence information has not helped in predicting the function of this molecule. 10 Our original aim was to identify new endothelial molecules involved in leukocyte trafficking. For this purpose, we raised monoclonal antibodies (mAbs) against small isolated vessels from the hilus of human lymph nodes. The expression pattern of one antibody showed striking specificity for endothelial cells, and, therefore, the antigen recognized by this antibody was selected for further characterization. Tryptic peptides and subsequent analyses of its cDNA showed homology of this antigen to rat PV-1 cDNA and a human cDNA designated fenestrated endothelial-linked structure protein (FELS). On the other hand, the similarities in the staining patterns between our antibody and PAL-E led to the present studies elucidating the identity of the molecule recognized by PAL-E. Materials and methods Production of the monoclonal antibodyBalb/C mice were immunized by injecting ...

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Endothelial cell marker PAL-E reactivity in brain tumor, developing brain, and brain disease

Cited by 31 publications

References 17 publications

The Endothelial Cell-Specific Antibody PAL-E Identifies a Secreted Form of Vimentin in the Blood Vasculature

The Endothelial Cell-Specific Antibody PAL-E Identifies a Secreted Form of Vimentin in the Blood Vasculature

Targeted Transport of 125I-Labeled Antibody to GFAP and AMVB1 in an Experimental Rat Model of C6 Glioma

Molecular identification of PAL-E, a widely used endothelial-cell marker

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