DOCSLIB.ORG

The Melanoma Tumor Antigen, Melanotransferrin (P97): a 25-Year Hallmark – from Iron Metabolism to Tumorigenesis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Melanoma Tumor Antigen, Melanotransferrin (P97): a 25-Year Hallmark – from Iron Metabolism to Tumorigenesis Oncogene (2007) 26, 6113–6124 & 2007 Nature Publishing Group All rights reserved 0950-9232/07 $30.00 www.nature.com/onc REVIEW The melanoma tumor antigen, melanotransferrin (p97): a 25-year hallmark – from iron metabolism to tumorigenesis Y Suryo Rahmanto, LL Dunn and DR Richardson Iron Metabolism and Chelation Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia Melanotransferrin (MTf) or melanoma tumor antigen p97 More recently, there have been reports of MTf is a transferrin (Tf) homolog that is found predominantly protein being identified in normal tissues, including bound to the cell membrane via a glycosyl phosphatidy- sweat gland ducts (Natali et al., 1987; Alemany et al., linositol anchor. The molecule is a member of the Tf 1993), avian eosinophils (McNagny et al., 1996), porcine superfamily and binds iron through a single high-affinity fetal intestinal epithelial cells (Danielsen and van Deurs, iron(III)-binding site. Since its discovery on the plasma 1995), liver endothelial cells (Sciot et al., 1989; Alemany membrane of melanoma cells, the function of MTf has et al., 1993), rabbit and mouse cartilage (Kawamoto remained intriguing, particularly in relation to its role in et al., 1998; Nakamasu et al., 1999), avian proximal cancer cell iron transport. In fact, considering the crucial kidney tubules (McNagny et al., 1996) and the normal role of iron in many metabolic pathways, e.g., DNA endothelium and reactive microglia of brains of synthesis, it was important to understand the function of Alzheimer’s disease (AD) patients (Jefferies et al., MTf in the transport of this vital nutrient. MTf has also 1996; Kennard et al., 1996; Rothenberger et al., 1996; been implicated in diverse physiological processes, such as Yamada et al., 1999). Normal sera contains very low plasminogen activation, angiogenesis and cell migration. levels of soluble MTf (sMTf) protein (Brown et al., However, recent studies using a knockout mouse and post- 1981b) and increased sMTf has been described in transcriptional gene silencing have demonstrated that patients with AD (Kennard et al., 1996) and arthritis MTf is not involved in iron metabolism, but plays a vital (Kato et al., 2001). In addition, MTf has been shown to role in melanoma cell proliferation and tumorigenesis. In be expressed at mRNA levels in a wide variety of human this review, we discuss the possible biological functions of tissues (Richardson, 2000).From a range of 50 normal MTf, particularly in relation to cancer. human tissues, the highest MTf mRNA levels were Oncogene (2007) 26, 6113–6124; doi:10.1038/sj.onc.1210442; found in the salivary gland (Richardson, 2000).Later published online 23 April 2007 studies in mice also demonstrated that MTf mRNA levels were high in this tissue as well as the pancreas and Keywords: melanotransferrin; tumorigenesis; iron meta- epididymis (Sekyere et al., 2005). Hence, the differential bolism; melanoma expression of MTf suggests a specific function that may have physiological and pathological indications. MTf shares many important characteristics with serum Tf, including: (i) a sequence homology of 37–39% with Introduction human serum Tf, human lactoferrin (Lf) and chicken Tf; (ii) the MTf gene is located on chromosome 3, as are Melanotransferrin (MTf), or melanoma-associated tumor those for Tf and the transferrin receptor 1 (TfR1); (iii) the antigen p97, is a membrane-bound glycoprotein that is presence of many disulfide bonds in MTf that are also a homolog of the transferrin (Tf) family of non-heme present in Tf and Lf; (iv) MTf has an N-terminal Fe- Fe-binding proteins (Brown et al., 1982). MTf was one of binding site that is identical to the N-lobe Fe-binding site the first cell-surface markers associated with melanoma found in serum Tf; and (v) isolated and purified MTf can (Brown et al., 1981a). In fact, it was previously described bind Fe from Fe(III) citrate complexes (Brown et al., as an oncofetal antigen, being expressed in only small 1981a, 1982; Rose et al., 1986; Richardson and Baker, quantities in normal tissues, but in much larger amounts 1991a; Baker et al., 1992; Food et al., 2002). These in neoplastic cells (especially malignant melanoma cells) observations suggested that MTf played a role in Fe and fetal tissues (Woodbury et al., 1980; Brown et al., transport. 1981b). The most obvious difference between MTf and serum Tf is that MTf is bound mainly to the cell membrane by a glycosyl phosphatidylinositol (GPI) anchor, whereas Tf is found free in the plasma (Alemany et al., 1993; Correspondence: Dr DR Richardson, Department of Pathology, Food et al., 1994; Kennard et al., 1995; Nakamasu et al., University of Sydney, Sydney, New South Wales, 2006 Australia. E-mail: [email protected] 1999; Yamada et al., 1999). The sMTf may also be Received 21 August 2006; revised 16 January 2007; accepted 23 February secreted from cells, although at very low levels (Food 2007; published online 23 April 2007 et al., 1994). Recent investigations have shown that Melanotransferrin: a 25-year hallmark Y Suryo Rahmanto et al 6114 deletion of the GPI-anchor via genetic engineering a much larger protein of 2031 amino acids (Table 1). resulted in a recombinant sMTf that was far less However, BLAT analysis (database version March effective than Tf at donating Fe to cells (Food et al., 2006) demonstrated the presence of extra sequence 2002).In addition, sMTf cannot be bound by the TfR1 within chimp MTf that corresponded to the human nor transferrin receptor 2 (TfR2), despite its high discs large homolog 1 (Drosophila, Dlg1) gene.Hence, structural homology to Tf (Food et al., 2002; Kawabata the large size of chimp MTf as reported in the NCBI et al., 2004). database (XM_526438; accessed July 2006) may not be Due to its high homology with Tf, its ability to bind representative of the actual gene.Only human MTf Fe and its high expression on melanoma cells, MTf was protein has been purified and characterized in detail hypothesized to play a role in Fe uptake by these tumor (Brown et al., 1981a, 1982) and the software predictions cells (Brown et al., 1982; Rose et al., 1986; Richardson of the size of other MTf family members (Table 1) must and Baker, 1990; Richardson, 2000).This was an be confirmed experimentally.An MTf-like gene has important idea to investigate, as Fe is critical for been identified in the fruit fly, Drosophila melanogaster, DNA synthesis and cancer cell proliferation (Kwok and also in the mosquito, Anopheles gambiae (Adams and Richardson, 2002; Kalinowski and Richardson, et al., 2000). However, unlike other members of the MTf 2005).Other reports have suggested that MTf could play family, these insect molecules show far lower homology a role in endothelial migration and angiogenesis (Sala to other MTf family members and the single Fe-binding et al., 2002), plasminogen activation (Demeule et al., site is not conserved (Sekyere and Richardson, 2000). 2003; Michaud-Levesque et al., 2006), differentiation Hence, the role of these MTf-like proteins in insect Fe (McNagny et al., 1996; Suardita et al., 2002), and metabolism is unclear. MTf may transcytose across the blood–brain barrier The MTf amino acid sequence data from all ten animal (Demeule et al., 2002). More recently, studies using the species known have been aligned and a phylogenetic tree MTf knockout (MTfÀ/À) mouse and melanoma cells constructed (Figure 1a) by the neighbor-joining method engineered to have low MTf expression suggest the (http://align.genome.jp/) (Nakamasu et al., 1999). Analy- molecule may have a role in proliferation and melanoma sis of this phylogenetic tree shows the relationship of the tumorigenesis (Dunn et al., 2006). In this review, we will ten MTf members compared with human Tf, Lf and chic- discuss the molecular character and expression of MTf ken ovoTf.MTf diverged from the other Tf’s at position and its potential biological roles, particularly in relation ‘X’, whereas fish and avian MTf diverged from mammals to melanoma tumorigenesis. at position ‘Y’ (Figure 1a).Additionally, it has been previously shown that MTf diverged from Tf after the divergence of vertebrates and invertebrates (Nakamasu Genomic and molecular organization of MTf et al., 1999). Hence, there is evidence that in evolutionary terms, MTf is more distantly related to serum Tf than The human MTf gene and its equivalent have been Lf (Lambert et al., 2005a, b). Considering this, it is cloned and characterized in several organisms (Table 1). possible that the molecular architecture of the Tf molecule To date, this gene has been identified in ten organisms, could be a useful scaffold for ‘building’ other molecules namely human, chimpanzee, rabbit, rhesus monkey, with different functions and this is explored further in cow, mouse, rat, dog, chicken and zebrafish, where the section 5. molecules share 46–88% protein homology to human MTf.Most of the genes for MTf family members are Chromosomal localization and gene structure of MTf predicted to encode molecules of 721–1540 amino acids The human MTf gene (also denoted as MFI2)is in length, whereas the chimp gene is predicted to encode localized to region q28–29 on the reverse strand of Table 1 Comparison of known MTf gene and protein sequences between species Name Organism Genbank acces- mRNA % Nucleotide Protein % protein Chromosome number sion no. (bp) similaritya (aa) similaritya MTf Tf TfR Human Homo sapiens NM_005929 2377 100 738 100 3 3 3 bNM_033316 1651 78 302 78 — — — Chimp Pan troglodytes cXM_526438 6096 64 2031 84 3 3 3 Rabbit Oryctolagus cuniculus AB010995 2388 86 736 86 —d —d —d Rhesus Macaca mulatta cXM_001096034 4623 89 1540 86 2 2 2 Cow Bos Taurus cXM_589607 2346 88 739 88 1 1 —d Mouse Mus musculus NM_013900 4158 82 738 83 16 9 16 Rat Rattus norvegicus cXM_237839 2462 82 738 84 11 8 11 Dog Canis familiaris cXM_545158 3582 79 1193 78 33 23 33 Chicken Gallus gallus NM_205207 3547 63 738 60 9 9 9 Zebrafish Danio rerio cXM_689207 3095 54 721 46 6 —d 2 Abbreviations: MTf, melanotransferrin; Tf, transferrin; TfR, transferrin receptor.
Load more

Recommended publications
  • Binding and Uptake of H-Ferritin Are Mediated by Human Transferrin Receptor-1
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Caltech Authors Binding and uptake of H-ferritin are mediated by human transferrin receptor-1 Li Lia, Celia J. Fanga,b, James C. Ryana,b, Eréne C. Niemib, José A. Lebrónc,1, Pamela J. Björkmanc,d,2, Hisashi Arasee, Frank M. Tortif, Suzy V. Tortig, Mary C. Nakamuraa,b, and William E. Seamana,b,h,2 aDepartment of Medicine, Veterans Administration Medical Center, San Francisco, CA 94121; bDepartment of Medicine, University of California, San Francisco, CA 94143; cDivision of Biology, California Institute of Technology, Pasadena, CA 91125; dHoward Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125; eDepartment of Immunochemistry, World Premier International Immunology Frontier Research Center and Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; fDepartment of Cancer Biology, Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157; gDepartment of Biochemistry, Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157; and hDepartment of Microbiology and Immunology, University of California, San Francisco, CA 94143 Contributed by Pamela J. Björkman, November 18, 2009 (sent for review October 5, 2009) − Ferritin is a spherical molecule composed of 24 subunits of two constant of ∼6.5 × 10 7 L/mol and ∼10,000 receptors sites per cell; types, ferritin H chain (FHC) and ferritin L chain (FLC). Ferritin stores subsequently, they endocytose HFt (13). Activated fresh lympho- iron within cells, but it also circulates and binds specifically and cytes also bind HFt (16), as do erythroid precursors, in which the saturably to a variety of cell types.
    [Show full text]
  • Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse
    Welcome to More Choice CD Marker Handbook For more information, please visit: Human bdbiosciences.com/eu/go/humancdmarkers Mouse bdbiosciences.com/eu/go/mousecdmarkers Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse CD3 CD3 CD (cluster of differentiation) molecules are cell surface markers T Cell CD4 CD4 useful for the identification and characterization of leukocytes. The CD CD8 CD8 nomenclature was developed and is maintained through the HLDA (Human Leukocyte Differentiation Antigens) workshop started in 1982. CD45R/B220 CD19 CD19 The goal is to provide standardization of monoclonal antibodies to B Cell CD20 CD22 (B cell activation marker) human antigens across laboratories. To characterize or “workshop” the antibodies, multiple laboratories carry out blind analyses of antibodies. These results independently validate antibody specificity. CD11c CD11c Dendritic Cell CD123 CD123 While the CD nomenclature has been developed for use with human antigens, it is applied to corresponding mouse antigens as well as antigens from other species. However, the mouse and other species NK Cell CD56 CD335 (NKp46) antibodies are not tested by HLDA. Human CD markers were reviewed by the HLDA. New CD markers Stem Cell/ CD34 CD34 were established at the HLDA9 meeting held in Barcelona in 2010. For Precursor hematopoetic stem cell only hematopoetic stem cell only additional information and CD markers please visit www.hcdm.org. Macrophage/ CD14 CD11b/ Mac-1 Monocyte CD33 Ly-71 (F4/80) CD66b Granulocyte CD66b Gr-1/Ly6G Ly6C CD41 CD41 CD61 (Integrin b3) CD61 Platelet CD9 CD62 CD62P (activated platelets) CD235a CD235a Erythrocyte Ter-119 CD146 MECA-32 CD106 CD146 Endothelial Cell CD31 CD62E (activated endothelial cells) Epithelial Cell CD236 CD326 (EPCAM1) For Research Use Only.
    [Show full text]
  • High Efficiency Blood-Brain Barrier Transport Using a VNAR Targeting the Transferrin Receptor 1 (Tfr1)
    bioRxiv preprint doi: https://doi.org/10.1101/816900; this version posted October 30, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Title: High efficiency blood-brain barrier transport using a VNAR targeting the Transferrin Receptor 1 (TfR1) Authors: Pawel Stocki§, Jaroslaw M Szary§, Charlotte LM Jacobsen¶, Mykhaylo Demydchuk§, Leandra Northall§, Torben Moos¶, Frank S Walsh§ and J Lynn Rutkowski§* §Ossianix, Inc, Stevenage Bioscience Catalyst, Gunnels Wood Rd, Stevenage, Herts, SG1 2FX, UK and 3675 Market St, Philadelphia, PA 19104, USA ¶Laboratory of Neurobiology, Department of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 3, 9220 Aalborg, Denmark Address correspondence to: *J. Lynn Rutkowski, PhD Ossianix, Inc, 3675 Market St., Philadelphia, PA 19104, USA Email: [email protected] Tel: +1(610)291-1724 A one-sentence summary: Development of highly efficient, TfR1 specific, cross-species reactive blood-brain barrier (BBB) shuttle based on shark single domain VNAR antibody. Definitions of all symbols, abbreviations, and acronyms: Transferrin Receptor 1 (TfR1), blood-brain barrier (BBB), Transferrin (Tf), central nervous system (CNS), Variable domain of New Antigen Receptors (VNAR), complementarity-determining region 3 (CDR3), room temperature (RT), size exclusion chromatography (SEC), human serum albumin (HSA), Neurotensin (NT), Immunohistochemistry (IHC), next generation sequencing (NGS), Pharmacokinetic (PK), blood-CSF barrier (BCSFB), Percentage injected dose (%ID), Area under the curve (AUC), attenuated effector function (AEF), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS- PAGE), Western blot (WB), intravenous (IV) 1 bioRxiv preprint doi: https://doi.org/10.1101/816900; this version posted October 30, 2019.
    [Show full text]
  • Mitochondrial Iron Metabolism and Its Role in Neurodegeneration
    Journal of Alzheimer’s Disease 20 (2010) S551–S568 S551 DOI 10.3233/JAD-2010-100354 IOS Press Review Mitochondrial Iron Metabolism and Its Role in Neurodegeneration Maxx P. Horowitza,b,c and J. Timothy Greenamyreb,c,d,∗ aMedical Scientist Training Program, University of Pittsburgh, Pittsburgh, PA, USA bCenter for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA cDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, USA dPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA Accepted 16 April 2010 Abstract. In addition to their well-established role in providing the cell with ATP, mitochondria are the source of iron-sulfur clusters (ISCs) and heme – prosthetic groups that are utilized by proteins throughout the cell in various critical processes. The post-transcriptional system that mammalian cells use to regulate intracellular iron homeostasis depends, in part, upon the synthesis of ISCs in mitochondria. Thus, proper mitochondrial function is crucial to cellular iron homeostasis. Many neurodegenerative diseases are marked by mitochondrial impairment, brain iron accumulation, and oxidative stress – pathologies that are inter- related. This review discusses the physiological role that mitochondria play in cellular iron homeostasis and, in so doing, attempts to clarify how mitochondrial dysfunction may initiate and/or contribute to iron dysregulation in the context of neurodegenerative disease. We review what is currently known about the entry of iron into mitochondria, the ways in which iron is utilized therein, and how mitochondria are integrated into the system of iron homeostasis in mammalian cells. Lastly, we turn to recent advances in our understanding of iron dysregulation in two neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease), and discuss the use of iron chelation as a potential therapeutic approach to neurodegenerative disease.
    [Show full text]
  • Propranolol-Mediated Attenuation of MMP-9 Excretion in Infants with Hemangiomas
    Supplementary Online Content Thaivalappil S, Bauman N, Saieg A, Movius E, Brown KJ, Preciado D. Propranolol-mediated attenuation of MMP-9 excretion in infants with hemangiomas. JAMA Otolaryngol Head Neck Surg. doi:10.1001/jamaoto.2013.4773 eTable. List of All of the Proteins Identified by Proteomics This supplementary material has been provided by the authors to give readers additional information about their work. © 2013 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable. List of All of the Proteins Identified by Proteomics Protein Name Prop 12 mo/4 Pred 12 mo/4 Δ Prop to Pred mo mo Myeloperoxidase OS=Homo sapiens GN=MPO 26.00 143.00 ‐117.00 Lactotransferrin OS=Homo sapiens GN=LTF 114.00 205.50 ‐91.50 Matrix metalloproteinase‐9 OS=Homo sapiens GN=MMP9 5.00 36.00 ‐31.00 Neutrophil elastase OS=Homo sapiens GN=ELANE 24.00 48.00 ‐24.00 Bleomycin hydrolase OS=Homo sapiens GN=BLMH 3.00 25.00 ‐22.00 CAP7_HUMAN Azurocidin OS=Homo sapiens GN=AZU1 PE=1 SV=3 4.00 26.00 ‐22.00 S10A8_HUMAN Protein S100‐A8 OS=Homo sapiens GN=S100A8 PE=1 14.67 30.50 ‐15.83 SV=1 IL1F9_HUMAN Interleukin‐1 family member 9 OS=Homo sapiens 1.00 15.00 ‐14.00 GN=IL1F9 PE=1 SV=1 MUC5B_HUMAN Mucin‐5B OS=Homo sapiens GN=MUC5B PE=1 SV=3 2.00 14.00 ‐12.00 MUC4_HUMAN Mucin‐4 OS=Homo sapiens GN=MUC4 PE=1 SV=3 1.00 12.00 ‐11.00 HRG_HUMAN Histidine‐rich glycoprotein OS=Homo sapiens GN=HRG 1.00 12.00 ‐11.00 PE=1 SV=1 TKT_HUMAN Transketolase OS=Homo sapiens GN=TKT PE=1 SV=3 17.00 28.00 ‐11.00 CATG_HUMAN Cathepsin G OS=Homo
    [Show full text]
  • Broad and Thematic Remodeling of the Surface Glycoproteome on Isogenic
    bioRxiv preprint doi: https://doi.org/10.1101/808139; this version posted October 17, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Broad and thematic remodeling of the surface glycoproteome on isogenic cells transformed with driving proliferative oncogenes Kevin K. Leung1,5, Gary M. Wilson2,5, Lisa L. Kirkemo1, Nicholas M. Riley2,4, Joshua J. Coon2,3, James A. Wells1* 1Department of Pharmaceutical Chemistry, UCSF, San Francisco, CA, USA Departments of Chemistry2 and Biomolecular Chemistry3, University of Wisconsin- Madison, Madison, WI, 53706, USA 4Present address Department of Chemistry, Stanford University, Stanford, CA, 94305, USA 5These authors contributed equally *To whom correspondence should be addressed bioRxiv preprint doi: https://doi.org/10.1101/808139; this version posted October 17, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract: The cell surface proteome, the surfaceome, is the interface for engaging the extracellular space in normal and cancer cells. Here We apply quantitative proteomics of N-linked glycoproteins to reveal how a collection of some 700 surface proteins is dramatically remodeled in an isogenic breast epithelial cell line stably expressing any of six of the most prominent proliferative oncogenes, including the receptor tyrosine kinases, EGFR and HER2, and downstream signaling partners such as KRAS, BRAF, MEK and AKT.
    [Show full text]
  • Chapter 3: Phenotypic Characterisation of Melanotransferin Knockout Mouse and Down-Regulation of Melanotransferrin in Melanoma Cells
    CHAPTER 3: PHENOTYPIC CHARACTERISATION OF MELANOTRANSFERIN KNOCKOUT MOUSE AND DOWN-REGULATION OF MELANOTRANSFERRIN IN MELANOMA CELLS “An ignorant person is one who doesn't know what you have just found out.” Will Rogers, 1879 - 1935 This Chapter is published in: 1. Sekyere, E.O., Dunn, L.L., Suryo Rahmanto, Y., and Richardson, D.R. (2006) Role of melanotransferrin in iron metabolism: studies using targeted gene disruption in vivo. Blood. 107(7):2599-601. IF 2006: 10.4 *Selected by the Editors of Blood as a Plenary Paper which this journal describes as “papers of exceptional scientific importance”. 2. Dunn, L.L., Sekyere, E.O., Suryo Rahmanto, Y., and Richardson, D.R. (2006) The function of melanotransferrin: a role in melanoma cell proliferation and tumorigenesis. Carcinogenesis. 27(11):2157-69. IF 2006: 5.3 54 3.1. Introduction Melanotransferrin or melanoma tumour antigen p97 is an iron (Fe)-binding transferrin (Tf) homologue originally identified at high levels in melanomas and other tumours, cell lines and foetal tissues [Brown et al. 1981a; Brown et al. 1982; Woodbury et al. 1980]. Initial studies found MTf to be absent or only slightly expressed in normal adult tissues [Brown et al. 1981a], while later investigations demonstrated MTf in a range of normal tissues [Alemany et al. 1993; Rothenberger et al. 1996; Sciot et al. 1989]. Recent studies showed MTf to be expressed at higher levels in the brain and epithelial surfaces of the salivary gland, pancreas, testis, kidney and sweat gland ducts compared with other normal tissues [Richardson 2000; Sekyere et al. 2005; Sekyere et al.
    [Show full text]
  • Flow Reagents Single Color Antibodies CD Chart
    CD CHART CD N° Alternative Name CD N° Alternative Name CD N° Alternative Name Beckman Coulter Clone Beckman Coulter Clone Beckman Coulter Clone T Cells B Cells Granulocytes NK Cells Macrophages/Monocytes Platelets Erythrocytes Stem Cells Dendritic Cells Endothelial Cells Epithelial Cells T Cells B Cells Granulocytes NK Cells Macrophages/Monocytes Platelets Erythrocytes Stem Cells Dendritic Cells Endothelial Cells Epithelial Cells T Cells B Cells Granulocytes NK Cells Macrophages/Monocytes Platelets Erythrocytes Stem Cells Dendritic Cells Endothelial Cells Epithelial Cells CD1a T6, R4, HTA1 Act p n n p n n S l CD99 MIC2 gene product, E2 p p p CD223 LAG-3 (Lymphocyte activation gene 3) Act n Act p n CD1b R1 Act p n n p n n S CD99R restricted CD99 p p CD224 GGT (γ-glutamyl transferase) p p p p p p CD1c R7, M241 Act S n n p n n S l CD100 SEMA4D (semaphorin 4D) p Low p p p n n CD225 Leu13, interferon induced transmembrane protein 1 (IFITM1). p p p p p CD1d R3 Act S n n Low n n S Intest CD101 V7, P126 Act n p n p n n p CD226 DNAM-1, PTA-1 Act n Act Act Act n p n CD1e R2 n n n n S CD102 ICAM-2 (intercellular adhesion molecule-2) p p n p Folli p CD227 MUC1, mucin 1, episialin, PUM, PEM, EMA, DF3, H23 Act p CD2 T11; Tp50; sheep red blood cell (SRBC) receptor; LFA-2 p S n p n n l CD103 HML-1 (human mucosal lymphocytes antigen 1), integrin aE chain S n n n n n n n l CD228 Melanotransferrin (MT), p97 p p CD3 T3, CD3 complex p n n n n n n n n n l CD104 integrin b4 chain; TSP-1180 n n n n n n n p p CD229 Ly9, T-lymphocyte surface antigen p p n p n
    [Show full text]
  • Investigation of the Underlying Hub Genes and Molexular Pathogensis in Gastric Cancer by Integrated Bioinformatic Analyses
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Investigation of the underlying hub genes and molexular pathogensis in gastric cancer by integrated bioinformatic analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract The high mortality rate of gastric cancer (GC) is in part due to the absence of initial disclosure of its biomarkers. The recognition of important genes associated in GC is therefore recommended to advance clinical prognosis, diagnosis and and treatment outcomes. The current investigation used the microarray dataset GSE113255 RNA seq data from the Gene Expression Omnibus database to diagnose differentially expressed genes (DEGs). Pathway and gene ontology enrichment analyses were performed, and a proteinprotein interaction network, modules, target genes - miRNA regulatory network and target genes - TF regulatory network were constructed and analyzed. Finally, validation of hub genes was performed. The 1008 DEGs identified consisted of 505 up regulated genes and 503 down regulated genes.
    [Show full text]
  • Identification of Key Genes of Papillary Thyroid Carcinoma by Integrated
    Identication of key genes of papillary thyroid carcinoma by integrated bioinformatics analysis Gang Xue Hebei North University Xu Lin Hebei North University Jingfang Wu ( [email protected] ) Da Pei Hebei North University Dong-Mei Wang Hebei North University Jing Zhang Hebei North University Wen-Jing Zhang Hebei North University Research article Keywords: RNA-Seq, papillary thyroid carcinoma, key gene, bioinformatics Posted Date: January 7th, 2020 DOI: https://doi.org/10.21203/rs.2.20264/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/22 Abstract Background:Papillary thyroid carcinoma (PTC) is one of the fastest-growing malignant tumor types of thyroid cancer. Therefore, identifying the interaction of genes in PTC is crucial for elucidating its pathogenesis and nding more specic molecular biomarkers. Methods:In this study, 4 pairs of PTC tissues and adjacent tissues were sequenced using RNA-Seq, and 3745 differentially expressed genes (DEGs) were screened. The results of GO and KEGG enrichment analysis indicate that the vast majority of DEGs may play a positive role in the development of cancer. Then, the signicant modules were analysed using Cytoscape software in the protein-protein interaction (PPI) network. Survival analysis, TNM analysis, and immune inltration analysis of key genes are all analyzed. And the expression of ADORA1, APOE and LPAR5 genes was veried by qPCR in papillary thyroid carcinoma compared to their matching adjacent tissues. Results: A total of 25 genes were identied as hub genes with nodes greater than 10. The expression of 25 key genes in PTC were veried by the GEPIA database, and the overall survival and disease free survival analyses of these key genes were conducted with Kaplan–Meier plots.
    [Show full text]
  • A Novel Therapeutic Target in Ovarian Cancer Debargha Basuli University of Connecticut - Storrs, [email protected]
    University of Connecticut OpenCommons@UConn Doctoral Dissertations University of Connecticut Graduate School 6-8-2016 Iron Addiction In Tumor Initiating Cells: A Novel Therapeutic Target In Ovarian Cancer Debargha Basuli University of Connecticut - Storrs, [email protected] Follow this and additional works at: https://opencommons.uconn.edu/dissertations Recommended Citation Basuli, Debargha, "Iron Addiction In Tumor Initiating Cells: A Novel Therapeutic Target In Ovarian Cancer" (2016). Doctoral Dissertations. 1248. https://opencommons.uconn.edu/dissertations/1248 Iron Addiction In Tumor Initiating Cells: A Novel Therapeutic` Target In Ovarian Cancer Debargha Basuli, M.D., PhD University of Connecticut, 2016 Ovarian cancer is a highly lethal malignancy that has not seen a major therapeutic advance in over 30 years. We demonstrate that ovarian cancer exhibits a targetable alteration in iron metabolism. Ferroportin (FPN), an iron efflux pump, is decreased and transferrin receptor (TFRC), an iron importer, is increased in ovarian cancer tissue. Expression of FPN and TFRC are strongly associated with patient survival. Ovarian cancer tumor-initiating cells demonstrate a similar profile of iron excess. Iron deprivation induced by desferroxamine, knockout of IRP2, or overexpression of FPN preferentially blocks growth of tumor initiating cells. Iron restriction inhibits invasion, synthesis of MMPs and IL6, and reduces intraperitoneal spread of tumor cells in vivo. Growth of ovarian tumors is inhibited by induction of ferroptosis, an iron-dependent form of cell death. Thus, enhanced levels of iron create a metabolic vulnerability that can be exploited therapeutically. We show that this dependence is already evident in the tumor initiating cell and creates a new therapeutic opportunity. Thus, alterations in iron import and export in ovarian cancer result in an iron acquisitive phenotype and an increase in metabolically available iron.
    [Show full text]
  • MONOCLONAL ANTIBODY to MOUSE CD71, TRANSFERRIN RECEPTOR 1 (TFRC) Clone ER-MP21
    MONOCLONAL ANTIBODY TO MOUSE CD71, TRANSFERRIN RECEPTOR 1 (TFRC) clone ER-MP21 Catalog no HM1085 (lot number and expiry date are indicated on the label) Description The monoclonal antibody ER-MP21 recognizes CD71, the transferrin receptor 1. CD71 is a 200 kDa glycoprotein composed of two identical, disulfide-linked chains. Each chain is capable of binding transferrin, an iron-transport molecule. Binding of transferrin to its receptor followed by endocytosis of the receptor-ligand complex is a major cellular iron-uptake mechanism. Iron uptake by the proliferating cell is essential for the iron-containing enzyme ribonucleotide reductase involved with DNA synthesis. CD71 is not only expressed by cycling cells, but also by cells that require iron for other iron-dependent proteins, such as the enzyme peroxidase in monocytes. Rapidly proliferating cells, as in malignancy, generally express CD71 abundantly. Furthermore, CD71 has been described as a marker of immature, proliferating T cells. The monoclonal antibody ER-MP21 inhibits proliferation and differentiation during early T cell development. ER-MP21 recognizes murine CD71, but does not compete with transferrin binding. Aliases TFRC, TFR1, T9, p90 Species Rat IgG2a Formulation 1 ml (100 µg/ml) 0.2 µm filtered antibody solution in PBS, containing 0.1% bovine serum Application F FC FS IA IF IP P W Yes ● ● ●a No ● N.D. ● ● ● ● a = Inhibition of biological activity N.D.= Not Determined; F = Frozen sections; FC = Flow Cytometry; FS = Functional Studies; IA = Immuno Assays; IF = Immuno Fluorescence; IP = Immuno Precipitation; P = Paraffin sections; W = Western blot Use For immunohistology, and flow cytometry, dilutions to be used depend on detection system applied.
    [Show full text]