DOCSLIB.ORG

KAI Expression Prevents IL-8-Mediated Endothelial Gap Formation in Late-Stage Melanomas

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
KAI Expression Prevents IL-8-Mediated Endothelial Gap Formation in Late-Stage Melanomas Oncogene (2014) 33, 2898–2908 & 2014 Macmillan Publishers Limited All rights reserved 0950-9232/14 www.nature.com/onc ORIGINAL ARTICLE CD82/KAI expression prevents IL-8-mediated endothelial gap formation in late-stage melanomas P Khanna1, C-Y Chung2, RI Neves2,3,4,5,6, GP Robertson2,3,4,7,8,9 and C Dong1,8 Melanoma cells facilitate endothelial gap formation, the first step during tumor transendothelial migration, which is mediated by both adhesion and endogenously produced chemokines (in particular, interleukin-8 (IL-8)). Tetraspanins are localized to the cell surface in cancer and participate in various functions including invasion of tissues mediated by secretion of cytokines and matrix metalloproteinases. However, little is known about the role of CD82 tetraspanins in malignant melanomas during cancer cell invasion. In this study, we investigated the functional importance of CD82 expression in melanoma-mediated gap formation by using cDNAs to induce CD82 expression in highly invasive melanoma cell lines. Results showed that CD82 expression inhibited melanoma cell-induced gap formation, melanoma cell extravasation in vitro and subsequent lung metastasis development in vivo. Mechanistic studies showed that inducible expression of CD82 in highly metastatic melanoma cells significantly increased p21 expression upon binding of Duffy antigen receptor group (DARC), inducing tumor cell senescence and interrupting IL-8-mediated vascular endothelial (VE)-cadherin disassembly. Taken together, these studies provide a rationale for using drug therapies that restore CD82 expression and inhibit IL-8 production to inhibit late-stage melanoma cell extravasation and subsequent metastasis development. Oncogene (2014) 33, 2898–2908; doi:10.1038/onc.2013.249; published online 22 July 2013 Keywords: melanoma metastasis; CD82; IL-8; adhesion INTRODUCTION Previous work has shown that CD82 binds to Duffy antigen Metastasis is a complex process requiring melanoma cell receptor/chemokine group (DARC), and furthermore, that DARC detachment from its primary location and migration through expression in endothelial cells is necessary for CD82-mediated 16,17 blood or circulatory systems to secondary sites. Once cancer cells tumor suppression. Binding of CD82 on tumor cells to DARC metastasize to reach distant organs, cancers become increasingly receptors on endothelial cells prevents invasion of CD82-positive difficult to treat using current therapies warranting the need tumor cells by inducing senescence in CD82 þ cells. DARC also to elucidate molecular mechanism during this process.1–3 One binds C–X–C and C–C cytokine receptors (including interleukin 16,18 important event during cancer metastasis is melanoma cell (IL)-8) secreted by highly metastatic melanoma cells. extravasation through the endothelial vessels, which requires4,5 IL-8 has been shown to be an important factor in mediating (i) the breakdown of vascular endothelial (VE)-cadherins to form tumor cell extravasation through endothelial cells and underlying 19,20 gaps, (ii) penetration of the endothelial barrier and (iii) migration extracellular matrix. IL-8 binds with high affinity to CXCR2 and 21,22 of tumor cells through blood vessels into tissues to form DARC rather than CXCR1. Studies in fibroblasts have shown metastatic lesions. These events are mediated by adhesion that knocking down DARC diminishes cell senescence and molecules, inflammatory cytokines and proteases that degrade increases tumor cell extravasation.18,23,24 In normal physiology, the underlying extracellular matrix.5–7 DARC on endothelial cells modulates IL-8 signaling by acting as a Tetraspanins are a family of membrane proteins present in all ‘chemokine sink’ where DARC binds to chemokines, but does not tissue types that have a vital role in a wide spectrum of biological activate downstream signaling pathways.25 During tumor-induced functions.8,9 In cancers, tetraspanins (including CD82) have a vital inflammation, excess secretion of IL-8 within the tumor role in cellular invasion, particularly during cell movement.10–12 microenvironment disrupts this homeostasis. In melanoma cells, Studies have found that expression levels of CD82 tetraspanins these effects are exacerbated by synergistic secretion of IL-8 from decrease in highly metastatic cancers, increasing tumor endothelial cells bound to melanoma cells, facilitating migration cell extravasation.13,14 While the metastatic-suppressive effects of melanoma cells through the blood vessels.26–31 Upon IL-8 of CD82 have been demonstrated in cell, animal and patient binding to CXCR2 receptors, signaling pathways such as models,12,13,15 the complex molecular mechanism by which CD82 phosphatidylinositol-3 kinase and/or p38 mitogen-activated expression suppresses tumor cell extravasation remains unclear. protein kinase are activated. This signaling cascade inhibits 1Department of Bioengineering, The Pennsylvania State University, University Park, PA, USA; 2Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA, USA; 3Department of Dermatology, The Pennsylvania State University College of Medicine, Hershey, PA, USA; 4Penn State Melanoma Therapeutic Program, The Pennsylvania State University College of Medicine, Hershey, PA, USA; 5Cutaneous Oncology Program, The Pennsylvania State University College of Medicine, Hershey, PA, USA; 6Department of Surgery, Division of Plastic Surgery, The Pennsylvania State University College of Medicine, Hershey, PA, USA; 7Department of Pathology, The Pennsylvania State University College of Medicine, Hershey, PA, USA; 8Pennsylvania State Melanoma Center, The Pennsylvania State University College of Medicine, Hershey, PA, USA and 9The Foreman Foundation for Melanoma Research, The Pennsylvania State University College of Medicine, Hershey, PA, USA. Correspondence: Professor C Dong, Department of Bioengineering, The Pennsylvania State University, 205 Hallowell Building, University Park, PA 16802, USA or Professor GP Robertson, Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. E-mail: [email protected] or [email protected] Received 22 November 2012; revised 23 March 2013; accepted 19 April 2013; published online 22 July 2013 Inhibition of IL-8-mediated endothelial gap formation by CD82/KAI P Khanna et al 2899 tumor cell senescence and trigger internalization of VE-cadherin western blot analysis (Figure 1e, right panels). As CD82 À cells junctions in the endothelial cells forming gaps on endothelial migrate under low shear stresses (0.625 dyn/cm2) rather than high monolayers.32–38 Although several studies have focused on shear stresses (2 dyn/cm2), these results show that CD82 mediates CD82 and DARC interactions, the role of CD82 in regulating IL-8 the motility and subsequent extravasation of tumor cells rather signaling remains unclear. than adhesion of tumor cells. However, the role of CD82 in tumor In melanoma cells, IL-8 binding to endothelial cells have an cell extravasation remains unknown. important role in regulating VE-cadherin disassembly via activa- CD82 expression in highly metastatic lines dramatically reduces tion of CXCR2 receptors.37 However, previous literature shows that in vitro gap formation. As VE-cadherin junctions serve as the ectopic expression of CXCR2 in tumor cells results in tumor cell primary mediators of endothelial permeability,37,41 we senescence.18 These studies show that during oncogene-induced hypothesized that CD82 regulates these endothelial junctions. senescence there is an increase in IL-8 that binds CXCR2 receptors Human umbilical vein endothelial cells (HUVECs) were grown to on tumor cells to reinforce tumor cell growth arrest 98–99% confluency on coverslips and cocultured with A375M and migration.18 In cancer cells, cell senescence can be reversed melanoma cells transfected with 3.1 vector or CD82 cDNAs. by knocking down CXCR2 expression.16,39 Although several Quantification of the total gap area shows a significant reduction studies have found that CD82 binding DARC induces tumor cell in the total gap area and gap sizes in cells transfected with CD82 senescence via a p21-dependent mechanism,40–47 the effects of (Figure 2a, left) compared with the control cases (3.1 vector), CD82 on IL-8 have not been elucidated. where total gap area and sizes of the gaps are much larger. In this work, we showed that ectopic CD82 expression These results lead to the conclusion that high levels of CD82 suppresses IL-8 secretion and that binding of CD82 tetraspanins expression prevented gap formation. Conversely, knocking down to DARC receptors interrupts IL-8 signaling in endothelial cells. The CD82 expression using small interfering RNA (siRNA) increases gap p21/Waf1 protein is a cyclin-dependent kinase inhibitor, which formation (Figure 2a, right). Gap formation is one important step binds active cyclin-dependent kinase 2 or cyclin-dependent kinase during tumor cell extravasation.37 We found that reintroducing 4 complexes.43,44 Inhibition of cyclin-dependent kinase complexes CD82 expression in highly invasive melanoma cells decreased prevents progression of cells through the G1 phase of the cell tumor cell extravasation through HUVEC monolayers after 4 h cycle, resulting in growth arrest of cells or cellular senescence. (Figure 2b, top and bottom left panels). CD82 expression in cells Consistent with previous work, melanoma cells expressing was analyzed using western blot analysis (Figure 2b, top and physiological levels of CD82 bound
Load more

Recommended publications
  • Dynamics Within Tetraspanin Pairs Affect MHC Class II Expression
    328 Research Article Dynamics within tetraspanin pairs affect MHC class II expression Tineke van den Hoorn, Petra Paul, Lennert Janssen, Hans Janssen and Jacques Neefjes* Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands *Author for correspondence ([email protected]) Accepted 11 August 2011 Journal of Cell Science 125, 328–339 ß 2012. Published by The Company of Biologists Ltd doi: 10.1242/jcs.088047 Summary Late endosomal multivesicular bodies (MVBs) are complicated organelles with various subdomains located at the limiting membrane and the internal vesicles (ILVs). ILVs accumulate tetraspanins such as CD63 and CD82 that might form protein assemblies, including major histocompatibility complex class II (MHC-II) and its chaperone human leukocyte antigen (HLA)-DM. Here, we studied the effect of four late endosomal tetraspanin proteins on MHC-II expression. Silencing CD9, CD63 and CD81 enhanced MHC-II expression whereas silencing CD82 did not. No effect on peptide loading was observed. Using confocal FRET technology, we measured the dynamics of CD63 and CD82 interaction with MHC-II and its chaperone HLA-DM. CD63–CD82 interactions remained unaltered in the two MVB subdomains whereas the interactions between CD63 or CD82 homologous pairs changed. CD63 stably associated with MHC- II, and CD82 with HLA-DM, on both MVB subdomains whereas the CD82–MHC-II and CD63–HLA-DM interactions changed. These data visualize for the first time the protein dynamics of tetraspanin assemblies in MVB
    [Show full text]
  • Pancancer Progression Human Vjune2017
    Gene Symbol Accession Alias/Prev Symbol Official Full Name AAMP NM_001087.3 - angio-associated, migratory cell protein ABI3BP NM_015429.3 NESHBP|TARSH ABI family, member 3 (NESH) binding protein ACHE NM_000665.3 ACEE|ARACHE|N-ACHE|YT acetylcholinesterase ACTG2 NM_001615.3 ACT|ACTA3|ACTE|ACTL3|ACTSG actin, gamma 2, smooth muscle, enteric ACVR1 NM_001105.2 ACTRI|ACVR1A|ACVRLK2|ALK2|FOP|SKR1|TSRI activin A receptor, type I ACVR1C NM_145259.2 ACVRLK7|ALK7 activin A receptor, type IC ACVRL1 NM_000020.1 ACVRLK1|ALK-1|ALK1|HHT|HHT2|ORW2|SKR3|TSR-I activin A receptor type II-like 1 ADAM15 NM_207195.1 MDC15 ADAM metallopeptidase domain 15 ADAM17 NM_003183.4 ADAM18|CD156B|CSVP|NISBD|TACE ADAM metallopeptidase domain 17 ADAM28 NM_014265.4 ADAM 28|ADAM23|MDC-L|MDC-Lm|MDC-Ls|MDCL|eMDC II|eMDCII ADAM metallopeptidase domain 28 ADAM8 NM_001109.4 CD156|MS2 ADAM metallopeptidase domain 8 ADAM9 NM_001005845.1 CORD9|MCMP|MDC9|Mltng ADAM metallopeptidase domain 9 ADAMTS1 NM_006988.3 C3-C5|METH1 ADAM metallopeptidase with thrombospondin type 1 motif, 1 ADAMTS12 NM_030955.2 PRO4389 ADAM metallopeptidase with thrombospondin type 1 motif, 12 ADAMTS8 NM_007037.4 ADAM-TS8|METH2 ADAM metallopeptidase with thrombospondin type 1 motif, 8 ADAP1 NM_006869.2 CENTA1|GCS1L|p42IP4 ArfGAP with dual PH domains 1 ADD1 NM_001119.4 ADDA adducin 1 (alpha) ADM2 NM_001253845.1 AM2|dJ579N16.4 adrenomedullin 2 ADRA2B NM_000682.4 ADRA2L1|ADRA2RL1|ADRARL1|ALPHA2BAR|alpha-2BAR adrenoceptor alpha 2B AEBP1 NM_001129.3 ACLP AE binding protein 1 AGGF1 NM_018046.3 GPATC7|GPATCH7|HSU84971|HUS84971|VG5Q
    [Show full text]
  • Aberrant Expression of Tetraspanin Molecules in B-Cell Chronic Lymphoproliferative Disorders and Its Correlation with Normal B-Cell Maturation
    Leukemia (2005) 19, 1376–1383 & 2005 Nature Publishing Group All rights reserved 0887-6924/05 $30.00 www.nature.com/leu Aberrant expression of tetraspanin molecules in B-cell chronic lymphoproliferative disorders and its correlation with normal B-cell maturation S Barrena1,2, J Almeida1,2, M Yunta1,ALo´pez1,2, N Ferna´ndez-Mosteirı´n3, M Giralt3, M Romero4, L Perdiguer5, M Delgado1, A Orfao1,2 and PA Lazo1 1Instituto de Biologı´a Molecular y Celular del Ca´ncer, Centro de Investigacio´n del Ca´ncer, Consejo Superior de Investigaciones Cientı´ficas-Universidad de Salamanca, Salamanca, Spain; 2Servicio de Citometrı´a, Universidad de Salamanca and Hospital Universitario de Salamanca, Salamanca, Spain; 3Servicio de Hematologı´a, Hospital Universitario Miguel Servet, Zaragoza, Spain; 4Hematologı´a-hemoterapia, Hospital Universitario Rı´o Hortega, Valladolid, Spain; and 5Servicio de Hematologı´a, Hospital de Alcan˜iz, Teruel, Spain Tetraspanin proteins form signaling complexes between them On the cell surface, tetraspanin antigens are present either as and with other membrane proteins and modulate cell adhesion free molecules or through interaction with other proteins.25,26 and migration properties. The surface expression of several tetraspanin antigens (CD9, CD37, CD53, CD63, and CD81), and These interacting proteins include other tetraspanins, integri- F 22,27–30F their interacting proteins (CD19, CD21, and HLA-DR) were ns particularly those with the b1 subunit HLA class II 31–33 34,35 analyzed during normal B-cell maturation and compared to a moleculesFeg HLA DR -, CD19, the T-cell recep- group of 67 B-cell neoplasias. Three patterns of tetraspanin tor36,37 and several other members of the immunoglobulin expression were identified in normal B cells.
    [Show full text]
  • Project 1: Investigating the Interaction Between the Tetraspanin CD82 And
    Investigating the Interaction between the Tetraspanin CD82 and Gangliosides And Investigating the Binding Partners of CLEC14A and the Function of the CLEC14A Extracellular Domain By Puja Lodhia A dissertation submitted to the University of Birmingham in partial fulfilment of the Degree of MRes Biomedical Research College of Medical and Dental Sciences University Of Birmingham Submitted August 2012 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. Investigating the Interaction Between the Tetraspanin CD82 and Gangliosides By Puja Lodhia A dissertation submitted to the University of Birmingham in partial fulfilment of the Degree of MRes Biomedical Research College of Medical and Dental Sciences University Of Birmingham Submitted August 2012 Abstract CD82 is a tetraspanin involved in tumour metastasis suppression. It is downregulated in several cancers including breast, liver and prostate cancer. Although interactions with gangliosides and cholesterol have been demonstrated, no ligand has yet been identified to directly target CD82. CD82 interaction with gangliosides has been explored by immunoprecipitation from cell lysates. However, direct interaction of purified full length CD82 protein with ganglioside has not yet been shown.
    [Show full text]
  • Expression of Tetraspanins in Human Lung Cancer Cells: Frequent Downregulation of CD9 and Its Contribution to Cell Motility in Small Cell Lung Cancer
    Oncogene (2003) 22, 674–687 & 2003 Nature Publishing Group All rights reserved 0950-9232/03 $25.00 www.nature.com/onc Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer Toshiki Funakoshi1, Isao Tachibana*,1, Yoshihiko Hoshida2, Hiromi Kimura1, Yoshito Takeda1, Takashi Kijima3, Kazumi Nishino1, Hiroyuki Goto1, Tsutomu Yoneda1, Toru Kumagai1, Tadashi Osaki1, Seiji Hayashi1, Katsuyuki Aozasa2 and Ichiro Kawase1 1Department of Molecular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Sutia, Osaka 565-0871, Japan; 2Department of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Sutia, Osaka 565-0871, Japan; 3Division of Thoracic and Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA Small cell lung cancer (SCLC) invades locally and lungcancer (SCLC) and nonsmall cell lungcancer metastasizes distantly extremely early when compared (NSCLC). SCLC is characterized by several neuroendo- with nonsmall cell lung cancer (NSCLC). The underlying crine features, as evidenced by the presence of dense core molecular mechanisms, however, have not been elucidated. granules, high enzymatic activities of L-dopa decarbox- Accumulating evidence suggests that downregulation of ylase, production of hormones and neuropeptides, and several members of tetraspanins is associated with expression of neural cell adhesion molecule (N-CAM) progression of solid tumors, thus indicating poor prog- (Carney et al., 1985). Clinically, SCLC is distinct from nosis. Here we screened 30 lung cancer cell lines for NSCLC in that most patients are inoperable at expression of tetraspanins, CD9, CD63, CD81, CD82, diagnosis, because the tumor locally invades and CD151, and NAG-2.
    [Show full text]
  • The Palmitoylation of Metastasis Suppressor KAI1/CD82 Is Important for Its Motility- and Invasiveness-Inhibitory Activity
    [CANCER RESEARCH 64, 7455–7463, October 15, 2004] The Palmitoylation of Metastasis Suppressor KAI1/CD82 Is Important for Its Motility- and Invasiveness-Inhibitory Activity Bin Zhou,1 Li Liu,1 Muralidhar Reddivari,1 and Xin A. Zhang1,2 1Vascular Biology Center and Department of Medicine and 2Department of Molecular Science, University of Tennessee Health Science Center, Memphis, Tennessee ABSTRACT (18) or tetraspanin-enriched microdomains (19, 20) in which tet- raspanins are associated with one another as well as with nontet- The cancer metastasis suppressor protein KAI1/CD82 is a member of raspanin transmembrane proteins such as integrins, growth factors, the tetraspanin superfamily. Recent studies have demonstrated that tet- and growth factor receptors (20–23). Associations between protein raspanins are palmitoylated and that palmitoylation contributes to the organization of tetraspanin webs or tetraspanin-enriched microdomains. components within the tetraspanin web likely include both protein- However, the effect of palmitoylation on tetraspanin-mediated cellular protein and protein-lipid-protein interactions (21, 24, 25). Participa- functions remains obscure. In this study, we found that tetraspanin KAI1/ tion of KAI1/CD82 in tetraspanin webs may affect the organization of CD82 was palmitoylated when expressed in PC3 metastatic prostate can- the tetraspanin webs and subsequently the functional status of growth cer cells and that palmitoylation involved all of the cytoplasmic cysteine factors, their receptors, and cell adhesion molecules in the webs. residues proximal to the plasma membrane. Notably, the palmitoylation- Formation of the tetraspanin web is apparently determined by the deficient KAI1/CD82 mutant largely reversed the wild-type KAI1/CD82’s intrinsic biochemical features of tetrapanins.
    [Show full text]
  • Cx3cr1 Mediates the Development of Monocyte-Derived Dendritic Cells During Hepatic Inflammation
    CX3CR1 MEDIATES THE DEVELOPMENT OF MONOCYTE-DERIVED DENDRITIC CELLS DURING HEPATIC INFLAMMATION. Supplementary material Supplementary Figure 1: Liver CD45+ myeloid cells were pre-gated for Ly6G negative cells for excluding granulocytes and HDCs subsequently analyzed among the cells that were CD11c+ and had high expression of MHCII. Supplementary Table 1 low/- high + Changes in gene expression between CX3CR1 and CX3CR1 CD11b myeloid hepatic dendritic cells (HDCs) from CCl4-treated mice high Genes up-regulated in CX3CR1 HDCs Gene Fold changes P value Full name App 4,01702 5,89E-05 amyloid beta (A4) precursor protein C1qa 9,75881 1,69E-22 complement component 1, q subcomponent, alpha polypeptide C1qb 9,19882 3,62E-20 complement component 1, q subcomponent, beta polypeptide Ccl12 2,51899 0,011769 chemokine (C-C motif) ligand 12 Ccl2 6,53486 6,37E-11 chemokine (C-C motif) ligand 2 Ccl3 4,99649 5,84E-07 chemokine (C-C motif) ligand 3 Ccl4 4,42552 9,62E-06 chemokine (C-C motif) ligand 4 Ccl6 3,9311 8,46E-05 chemokine (C-C motif) ligand 6 Ccl7 2,60184 0,009272 chemokine (C-C motif) ligand 7 Ccl9 4,17294 3,01E-05 chemokine (C-C motif) ligand 9 Ccr2 3,35195 0,000802 chemokine (C-C motif) receptor 2 Ccr5 3,23358 0,001222 chemokine (C-C motif) receptor 5 Cd14 6,13325 8,61E-10 CD14 antigen Cd36 2,94367 0,003243 CD36 antigen Cd44 4,89958 9,60E-07 CD44 antigen Cd81 6,49623 8,24E-11 CD81 antigen Cd9 3,06253 0,002195 CD9 antigen Cdkn1a 4,65279 3,27E-06 cyclin-dependent kinase inhibitor 1A (P21) Cebpb 6,6083 3,89E-11 CCAAT/enhancer binding protein (C/EBP),
    [Show full text]
  • Human CD Marker Chart Reviewed by HLDA1 Bdbiosciences.Com/Cdmarkers
    BD Biosciences Human CD Marker Chart Reviewed by HLDA1 bdbiosciences.com/cdmarkers 23-12399-01 CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD1a R4, T6, Leu6, HTA1 b-2-Microglobulin, CD74 + + + – + – – – CD93 C1QR1,C1qRP, MXRA4, C1qR(P), Dj737e23.1, GR11 – – – – – + + – – + – CD220 Insulin receptor (INSR), IR Insulin, IGF-2 + + + + + + + + + Insulin-like growth factor 1 receptor (IGF1R), IGF-1R, type I IGF receptor (IGF-IR), CD1b R1, T6m Leu6 b-2-Microglobulin + + + – + – – – CD94 KLRD1, Kp43 HLA class I, NKG2-A, p39 + – + – – – – – – CD221 Insulin-like growth factor 1 (IGF-I), IGF-II, Insulin JTK13 + + + + + + + + + CD1c M241, R7, T6, Leu6, BDCA1 b-2-Microglobulin + + + – + – – – CD178, FASLG, APO-1, FAS, TNFRSF6, CD95L, APT1LG1, APT1, FAS1, FASTM, CD95 CD178 (Fas ligand) + + + + + – – IGF-II, TGF-b latency-associated peptide (LAP), Proliferin, Prorenin, Plasminogen, ALPS1A, TNFSF6, FASL Cation-independent mannose-6-phosphate receptor (M6P-R, CIM6PR, CIMPR, CI- CD1d R3G1, R3 b-2-Microglobulin, MHC II CD222 Leukemia
    [Show full text]
  • CD82, but Not CD63, Is Linked to Cellular Invasiveness in Human Thyroid Carcinoma
    Aus der Universitätsklinik und Poliklinik für Kinderchirurgie an der Martin-Luther-Universität Halle-Wittenberg (Direktor: Prof. Dr. med. Rainer Finke) und der Universitätsklinik und Poliklinik für Allgemein-, Viszeral- und Gefäßchirurgie an der Martin-Luther-Universität Halle-Wittenberg (Direktor: Prof. Dr. med. Henning Dralle) CD82, but not CD63, is linked to cellular invasiveness in human thyroid carcinoma Dissertation zur Erlangung des akademischen Grades Doktor der Medizin (Dr. med.) vorgelegt der Medizinischen Fakultät der Martin-Luther-Universität Halle-Wittenberg von Zhouxun Chen geboren am 21.06.1974 in Zhejiang, VR China Gutachter: 1. Prof. Dr. med. Rainer Finke (MLU, Halle) 2. PD. Dr. rer. nat. Cornelia Schmutzler (Charité, Berlin) 3. PD. Dr. med. Sabine Hombach-Klonisch (Manitoba, Canada) Eröffnungsdatum des Promotionsverfahrens: 21.09.2006 Datum der öffentlichen Verteidigung: 24.01.2007 urn:nbn:de:gbv:3-000011259 [http://nbn-resolving.de/urn/resolver.pl?urn=nbn%3Ade%3Agbv%3A3-000011259] - II - Meinen Eltern - III - Referat und bibliographische Beschreibung In der vorliegenden experimentellen Arbeit wurde die Bedeutung der Tetraspanine CD82 und CD63 (transmembrane-4-superfamily -TM4SF) für das Wachstum der menschlichen Schilddrüsenkarzinome und für die Ausbildung von Metastasen untersucht. In verschiedenen soliden Tumoren des Menschen spielt CD82 eine wichtige Rolle in den Prozessen der Zelldifferenzierung, der Apoptose, der Zelladhäsion sowie der Metasta- sierung. Es ist bekannt, dass CD82 in Prostatakarzinomen die Ausbildung von Metastasen unterdrückt, dass CD63 die Motilität maligner Melanomzellen reguliert und in die Prozesse der Zelladhäsion involviert ist. Die mRNA- und die Proteinexpression der Tetraspanine CD82 und CD63 wurde mit Hilfe der RT-PCR und der Immunhistochemie in 75 malignen Schilddrüsengeweben (24 FTC, 33 PTC, 18 UTC) sowie in 12 benignen Veränderungen der Schilddrüse (Struma colloides et nodosa) be- stimmt.
    [Show full text]
  • Proteomic Analysis of Urinary Microvesicles and Exosomes in Medullary Sponge
    Supplemental material is neither peer-reviewed nor thoroughly edited by CJASN. The authors alone are responsible for the accuracy and presentation of the material. Proteomic analysis of urinary microvesicles and exosomes in medullary sponge kidney disease and autosomal dominant polycystic kidney disease Maurizio Bruschi1*, Simona Granata2*, Laura Santucci1*, Giovanni Candiano1, Antonia Fabris2, Nadia Antonucci2, Andrea Petretto3, Martina Bartolucci3, Genny Del Zotto3, Francesca Antonini3, Gian Marco Ghiggeri4, Antonio Lupo2, Giovanni Gambaro2, Gianluigi Zaza2 1 Laboratory on Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 2 Renal Unit, Department of Medicine, University-Hospital of Verona, Italy 3 Core Facilities, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 4 Division of Nephrology, Dialysis and Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 1 Supplemental material is neither peer-reviewed nor thoroughly edited by CJASN. The authors alone are responsible for the accuracy and presentation of the material. Table of contents for supplemental materials Supplemental methods Supplemental Figure 1. Age and eGFR of all study partecipants included in the study. Supplemental Figure 2. Characterization of isolated exosomes and microvesicles Supplemental Figure 3. Gene Ontology annotation of urinary extracellular vesicle proteins. Supplemental Figure 4. Multidimensional scaling analysis of extracellular vesicles from the urine of medullary sponge kidney (MSK) and autosomal dominant polycystic kidney disease
    [Show full text]
  • CD82 Suppresses ADAM17-Dependent E-Cadherin Cleavage and Cell Migration in Prostate Cancer
    Hindawi Disease Markers Volume 2020, Article ID 8899924, 10 pages https://doi.org/10.1155/2020/8899924 Research Article CD82 Suppresses ADAM17-Dependent E-Cadherin Cleavage and Cell Migration in Prostate Cancer Zhenkun Ma,1 Ye Gao,2 Wei Liu,1 Long Zheng,1 Ben Jin,1 Bei Duan,3 Hongjun Xie,1 Peng Guo,1 Jin Zeng,1 Ke Wang,1 Shan Xu,1 Xinyang Wang,1 Dalin He,1 and Lei Li 1 1Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an 710061, China 2Department of Emergency, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an 710061, China 3Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine, 5 Weiyang West Road, Xianyang 712000, China Correspondence should be addressed to Lei Li; [email protected] Received 21 August 2020; Revised 17 September 2020; Accepted 13 October 2020; Published 2 November 2020 Academic Editor: Jian Ma Copyright © 2020 Zhenkun Ma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. CD82 acts as a tumor suppressor in a series of steps in malignant progression. Here, we identified a novel function of CD82 on posttranslational regulating E-cadherin in prostate cancer. In our study, the declined expression of CD82 was verified in prostate cancer tissues and cell lines compared with normal tissue and cell lines. Functionally, CD82 inhibited cell migration and E- cadherin cleavage from the cell membrane in prostate cancer cell.
    [Show full text]
  • A Decrease in the Expression of CD63 Tetraspanin Protein Elevates Invasive Potential of Human Melanoma Cells
    EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 35, No. 4, 317-323, August 2003 A decrease in the expression of CD63 tetraspanin protein elevates invasive potential of human melanoma cells Hwa-In Jang1 and Hansoo Lee1,2 Yanez-Mo et al., 2001, for reviews). The tetraspanin molecules have been implicated in diverse biological 1Vascular System Research Center phenomena, including cell proliferation, activation, ad- Division of Life Sciences hesion, migration, differentiation, and development. Kangwon National University Some of these molecules have also been implicated Chunchon 200-701, Korea in cancer metastasis: CD9 expression is inversely 2Corresponding author: Tel, 82-33-250-8530; correlated with the appearance of metastases in Fax, 82-33-251-3990; E-mail, [email protected] melanomas, breast, lung, and colon cancers (Si and Hersey, 1993; Miyake et al., 1995; Adachi et al., Accepted 22 July 2003 1998; Mori et al., 1998). CD82, which was redis- covered as the KAI1 metastasis-suppressor gene pro- Abbreviations: ECM, extracellular matrix; MMP, matrix metallopro- duct, also become down-regulated in the malignant teinase; TM4SF, transmembrane 4 superfamily progression of many types of human cancers, includ- ing prostate, breast, pancreatic, lung, bladder, and gastric cancer (Guo et al., 1996; Ueda et al., 1996; Yang et al., 1997; Yu et al., 1997; Higashiyama et Abstract al., 1998; Hinoda et al., 1998). Several transfection CD63, which belongs to the tetraspanin membrane studies have demonstrated the metastasis-suppres- sing role of CD9 and CD82 in cancer cells (Ikeyama proteins, has been proposed to play an important et al., 1993; Dong et al., 1995; Takaoka et al., 1998a; role in inhibiting melanoma metastasis.
    [Show full text]