Upregulation of tumour endothelial marker-8 by interleukin-1β and its impact in IL-1β induced angiogenesis

Rmali, Khaled A.; Al-Rawi, Mahir A.; Parr, Christian; Puntis, M. C. A.; Jiang, Wen Guo

doi:10.3892/ijmm.14.1.75

Cited by 20 publications

(25 citation statements)

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“…ANTXR1, however, is prevalently expressed in cancer cells (65)(66)(67), particularly up-regulated in human colorectal cancer endothelium (68), suggesting it as a potential tumor target. Therefore, targeting CTSB or autophagy could be a useful therapeutic strategy for reducing the toxic effects of LeTx without affecting its anti-tumor activity.…”

Section: Discussionmentioning

confidence: 99%

Cathepsin B-mediated Autophagy Flux Facilitates the Anthrax Toxin Receptor 2-mediated Delivery of Anthrax Lethal Factor into the Cytoplasm

Ham

Mogridge

et al. 2010

Journal of Biological Chemistry

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Anthrax lethal toxin (LeTx) is a virulence factor secreted byBacillus anthracis and has direct cytotoxic effects on most cells once released into the cytoplasm. The cytoplasmic delivery of the proteolytically active component of LeTx, lethal factor (LF), is carried out by the transporter component, protective antigen, which interacts with either of two known surface receptors known as anthrax toxin receptor (ANTXR) 1 and 2. We found that the cytoplasmic delivery of LF by ANTXR2 was mediated by cathepsin B (CTSB) and required lysosomal fusion with LeTxcontaining endosomes. Also, binding of protective antigen to ANXTR1 or -2 triggered autophagy, which facilitated the cytoplasmic delivery of ANTXR2-associated LF. We found that whereas cells treated with the membrane-permeable CTSB inhibitor CA074-Me-or CTSB-deficient cells had no defect in fusion of LC3-containing autophagic vacuoles with lysosomes, autophagic flux was significantly delayed. These results suggested that the ANTXR2-mediated cytoplasmic delivery of LF was enhanced by CTSB-dependent autophagic flux. Anthrax lethal toxin (LeTx)2 and edema toxin are two key virulence factors secreted by Bacillus anthracis, the causative agent of anthrax (1, 2). LeTx and edema toxin are composed of lethal factor (LF) or edema factor (EF), respectively, and protective antigen (PA), which functions as a cytoplasmic transporter of LF or EF. These toxins are main contributors to the clinical manifestations of anthrax and are cytotoxic to host cells once delivered into the cytoplasm. EF is an adenylate cyclase that raises cAMP levels in cells (3). LF is a metalloproteinase that targets the N-terminal end of the mitogen-activated protein kinase kinase 1-7 (MEK1-7) (except MEK5) (4 -6) and in certain mouse cells induces pyronecrosis by activating NACHTleucine-rich repeat and pyrin domain-containing protein 1b (NALP1b) (7).Incorporation of LF or EF into the cytoplasm is initiated by the binding of PA to the host cell surface through interacting with either of two known receptors: anthrax receptor 1 (ANTXR1, also known as the tumor endothelial marker 8) (8) and ANTXR2 (also known as the capillary morphogenesis gene-2) (9). Both ANTXR1 and -2 are widely distributed in human tissues and share molecular and biochemical similarities in their extracellular PA interacting domains known as von Willebrand factor A or integrin-like inserted (I) domain (10), post-translational modifications such as palmitoylation and ubiquitination of cytoplasmic domains (11), and associations with the co-receptor lipoprotein receptor-related 6 molecule (12, 13). ANTXR1 and -2 are also distinct in that ANTXR1 is highly expressed in tumor endothelial and cancer cells, and ANTXR2 has a higher binding affinity to PA and requires a lower pH to form a transmembrane pore than ANTXR1 (10,14).After binding PA to either ANTXR, a furin-like surface protease then cleaves PA at the N-terminal end to release a 20-kDa soluble fragment, yielding membrane-associated 63-kDa PA (PA 63 ) that forms a ring-shape heptameric ...

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Section: Discussionmentioning

confidence: 99%

Cathepsin B-mediated Autophagy Flux Facilitates the Anthrax Toxin Receptor 2-mediated Delivery of Anthrax Lethal Factor into the Cytoplasm

Ham

Mogridge

et al. 2010

Journal of Biological Chemistry

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“…Two von Willebrand factor A-like domain-containing receptors for PA have been characterized: tumor endothelial marker 8 and capillary morphogenesis protein 2 (8,23). Tumor endothelial marker 8 is highly expressed in epithelial cells lining B. anthracis entry sites and tumor vasculature, whereas capillary morphogenesis protein 2 is expressed in most human cells (6,22). Lethal toxin (LT) (PA plus LF) and the toxin ET (PA plus EF) have different effects during B. anthracis-induced animal death.…”

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confidence: 99%

Injection of Staphylococcus aureus EDIN by the Bacillus anthracis Protective Antigen Machinery Induces Vascular Permeability

et al. 2009

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Systemic injection of Bacillus anthracis lethal toxin (LT) produces vascular leakage and animal death. Recent studies suggest that LT triggers direct endothelial cell cytotoxicity that is responsible for the vascular leakage. LT is composed of heptamers of protective antigen (PA), which drives the endocytosis and translocation into host cells of the lethal factor (LF), a mitogen-activated protein kinase kinase protease. Here we investigated the consequences of injection of an endothelium-permeabilizing factor using LT as a "molecular syringe." To this end, we generated the chimeric factor LE, corresponding to the PA-binding domain of LF (LF 1-254 ) fused to EDIN exoenzyme. EDIN ADP ribosylates RhoA, leading to actin cable disruption and formation of transcellular tunnels in endothelial cells. We report that systemic injection of LET (LE plus PA) triggers a PAdependent increase in the pulmonary endothelium permeability. We also report that native LT induces a progressive loss of endothelium barrier function. We established that there is a direct correlation between the extent of endothelium permeability induced by LT and the cytotoxic activity of LT. This suggests new ways to design therapeutic drugs against anthrax directed toward vascular permeability.

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“…In extracellular region, TEM-8 has the von Willebrand factor type A domain containing a metal ion-dependent adhesion motif (I-domain) [36,37]. The TEM8 domain is most similar to that of D integrin, which has been shown to interact with vascular cell adhesion molecule via its I-domain during leukocyte trafficking [37][38][39]. TEM-8 proved to be consistently expressed at very low levels or below detection in normal tissues, but is expressed at significant levels in tumor tissues [15,16].…”

Section: Discussionmentioning

confidence: 99%

Detection of Epithelial Cells by RT-PCR Targeting CEA, CK20, and TEM-8 in Colorectal Carcinoma Patients Using OncoQuick Density Gradient Centrifugation System

Lagoudianakis

Kataki

Manouras

et al. 2009

Journal of Surgical Research

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Upregulation of tumour endothelial marker-8 by interleukin-1β and its impact in IL-1β induced angiogenesis

Cited by 20 publications

References 0 publications

Cathepsin B-mediated Autophagy Flux Facilitates the Anthrax Toxin Receptor 2-mediated Delivery of Anthrax Lethal Factor into the Cytoplasm

Cathepsin B-mediated Autophagy Flux Facilitates the Anthrax Toxin Receptor 2-mediated Delivery of Anthrax Lethal Factor into the Cytoplasm

Injection of Staphylococcus aureus EDIN by the Bacillus anthracis Protective Antigen Machinery Induces Vascular Permeability

Detection of Epithelial Cells by RT-PCR Targeting CEA, CK20, and TEM-8 in Colorectal Carcinoma Patients Using OncoQuick Density Gradient Centrifugation System

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