{{Short description|Protein which in humans is encoded by the SDC1 gene}} {{Infobox_gene}}
'''Syndecan 1''' is a protein which in humans is encoded by the ''SDC1'' gene.<ref name="pmid2324102">{{cite journal | vauthors = Mali M, Jaakkola P, Arvilommi AM, Jalkanen M | title = Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans | journal = The Journal of Biological Chemistry | volume = 265 | issue = 12 | pages = 6884–6889 | date = April 1990 | pmid = 2324102 | doi = 10.1016/S0021-9258(19)39232-4 | doi-access = free }}</ref><ref name="pmid2173154">{{cite journal | vauthors = Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J | title = Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2 | journal = Somatic Cell and Molecular Genetics | volume = 16 | issue = 5 | pages = 501–505 | date = September 1990 | pmid = 2173154 | doi = 10.1007/BF01233200 | s2cid = 43270934 }}</ref> The protein is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Syndecan-1 is a sponge for growth factors and chemokines,<ref>{{cite journal | vauthors = Götte M | title = Syndecans in inflammation | journal = FASEB Journal | volume = 17 | issue = 6 | pages = 575–591 | date = April 2003 | pmid = 12665470 | doi = 10.1096/fj.02-0739rev | doi-access = free | s2cid = 16948257 }}</ref> with binding largely via heparan sulfate chains. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein.
Altered syndecan-1 expression has been detected in several different tumor types. Syndecan 1 can be a marker for plasma cells.
== Structure ==
The syndecan-1 core protein consists of an extracellular domain which can be substituted with heparan sulfate and chondroitin sulfate glycosaminoglycan chains, a highly conserved transmembrane domain, and a highly conserved cytoplasmic domain, which contains two constant regions that are separated by a variable region.<ref>{{cite journal | vauthors = Bernfield M, Götte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M | title = Functions of cell surface heparan sulfate proteoglycans | journal = Annual Review of Biochemistry | volume = 68 | pages = 729–777 | date = 1999 | pmid = 10872465 | doi = 10.1146/annurev.biochem.68.1.729 }}</ref> The extracellular domain can be cleaved (shed) from the cell surface at a juxtamembrane site,<ref>{{cite journal | vauthors = Wang Z, Götte M, Bernfield M, Reizes O | title = Constitutive and accelerated shedding of murine syndecan-1 is mediated by cleavage of its core protein at a specific juxtamembrane site | journal = Biochemistry | volume = 44 | issue = 37 | pages = 12355–12361 | date = September 2005 | pmid = 16156648 | pmc = 2546870 | doi = 10.1021/bi050620i }}</ref> converting the membrane-bound proteoglycan into a paracrine effector molecule with roles in wound repair <ref>{{cite journal | vauthors = Elenius V, Götte M, Reizes O, Elenius K, Bernfield M | title = Inhibition by the soluble syndecan-1 ectodomains delays wound repair in mice overexpressing syndecan-1 | journal = The Journal of Biological Chemistry | volume = 279 | issue = 40 | pages = 41928–41935 | date = October 2004 | pmid = 15220342 | doi = 10.1074/jbc.M404506200 | doi-access = free }}</ref> and invasive growth of cancer cells.<ref>{{cite journal | vauthors = Piperigkou Z, Mohr B, Karamanos N, Götte M | title = Shed proteoglycans in tumor stroma | journal = Cell and Tissue Research | volume = 365 | issue = 3 | pages = 643–655 | date = September 2016 | pmid = 27365088 | doi = 10.1007/s00441-016-2452-4 | s2cid = 13944019 | url = https://zenodo.org/record/3375516 }}</ref>
An exception is the prosecretory mitogen lacritin that binds syndecan-1 only after heparanase modification.<ref name="pmid16982797">{{cite journal | vauthors = Ma P, Beck SL, Raab RW, McKown RL, Coffman GL, Utani A, Chirico WJ, Rapraeger AC, Laurie GW | display-authors = 6 | title = Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin | journal = The Journal of Cell Biology | volume = 174 | issue = 7 | pages = 1097–1106 | date = September 2006 | pmid = 16982797 | pmc = 1666580 | doi = 10.1083/jcb.200511134 }}</ref><ref name="pmid23504321 [PubMed - indexed for MEDLINE]">{{cite journal | vauthors = Zhang Y, Wang N, Raab RW, McKown RL, Irwin JA, Kwon I, van Kuppevelt TH, Laurie GW | display-authors = 6 | title = Targeting of heparanase-modified syndecan-1 by prosecretory mitogen lacritin requires conserved core GAGAL plus heparan and chondroitin sulfate as a novel hybrid binding site that enhances selectivity | journal = The Journal of Biological Chemistry | volume = 288 | issue = 17 | pages = 12090–12101 | date = April 2013 | pmid = 23504321 | pmc = 3636894 | doi = 10.1074/jbc.M112.422717 | doi-access = free }}</ref> Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelial heparanase (HPSE) cleaves off heparan sulfate to expose a binding site in the N-terminal region of syndecan-1's core protein.<ref name="pmid16982797" /> Three SDC1 elements are required. (1) The heparanase-exposed hydrophobic sequence GAGAL that promotes the alpha helicity of lacritin's C-terminal amphipathic alpha helix form and likely binds to the hydrophobic face. (2) Heparanase-cleaved heparan sulfate that is 3-O sulfated.<ref name="pmid23504321 [PubMed - indexed for MEDLINE]" /> This likely interacts with the cationic face of lacritin's C-terminal amphipathic alpha helix. (3) An N-terminal chondroitin sulfate chain that also likely binds to the cationic face. Point mutagenesis of lacritin has narrowed the ligation site.<ref name="pmid23504321 [PubMed - indexed for MEDLINE]" />
While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein.<ref>{{cite web | title = Entrez Gene: SDC1 syndecan 1| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=6382}}</ref>
==Inflammation == Syndecan-1 deficient mice show increased inflammation, which was attributed to an increased ICAM-1 and heparan sulfate-dependent recruitment of leukocytes (including neutrophils and dendritic cells)<ref>{{cite journal | vauthors = Averbeck M, Kuhn S, Bühligen J, Götte M, Simon JC, Polte T | title = Syndecan-1 regulates dendritic cell migration in cutaneous hypersensitivity to haptens | journal = Experimental Dermatology | volume = 26 | issue = 11 | pages = 1060–1067 | date = November 2017 | pmid = 28453867 | doi = 10.1111/exd.13374 | s2cid = 38757296 }}</ref> to the inflamed endothelium.<ref>{{cite journal | vauthors = Götte M, Joussen AM, Klein C, Andre P, Wagner DD, Hinkes MT, Kirchhof B, Adamis AP, Bernfield M | display-authors = 6 | title = Role of syndecan-1 in leukocyte-endothelial interactions in the ocular vasculature | journal = Investigative Ophthalmology & Visual Science | volume = 43 | issue = 4 | pages = 1135–1141 | date = April 2002 | pmid = 11923257 | url = https://iovs.arvojournals.org/article.aspx?articleid=2200171 }}</ref> This increase results in higher inflammatory responses and tissue damage in experimental models of contact dermatitis,<ref>{{cite journal | vauthors = Kharabi Masouleh B, Ten Dam GB, Wild MK, Seelige R, van der Vlag J, Rops AL, Echtermeyer FG, Vestweber D, van Kuppevelt TH, Kiesel L, Götte M | display-authors = 6 | title = Role of the heparan sulfate proteoglycan syndecan-1 (CD138) in delayed-type hypersensitivity | journal = Journal of Immunology | volume = 182 | issue = 8 | pages = 4985–4993 | date = April 2009 | pmid = 19342678 | doi = 10.4049/jimmunol.0800574 | doi-access = free }}</ref> inflammation of the kidney,<ref>{{cite journal | vauthors = Rops AL, Götte M, Baselmans MH, van den Hoven MJ, Steenbergen EJ, Lensen JF, Wijnhoven TJ, Cevikbas F, van den Heuvel LP, van Kuppevelt TH, Berden JH, van der Vlag J | display-authors = 6 | title = Syndecan-1 deficiency aggravates anti-glomerular basement membrane nephritis | journal = Kidney International | volume = 72 | issue = 10 | pages = 1204–1215 | date = November 2007 | pmid = 17805240 | doi = 10.1038/sj.ki.5002514 | doi-access = free }}</ref> myocardial infarction,<ref>{{cite journal | vauthors = Vanhoutte D, Schellings MW, Götte M, Swinnen M, Herias V, Wild MK, Vestweber D, Chorianopoulos E, Cortés V, Rigotti A, Stepp MA, Van de Werf F, Carmeliet P, Pinto YM, Heymans S | display-authors = 6 | title = Increased expression of syndecan-1 protects against cardiac dilatation and dysfunction after myocardial infarction | journal = Circulation | volume = 115 | issue = 4 | pages = 475–482 | date = January 2007 | pmid = 17242279 | doi = 10.1161/CIRCULATIONAHA.106.644609 | doi-access = free | url = https://lirias.kuleuven.be/bitstream/123456789/24985/1/SDC1-MMI%20d%20vanhoutte%20et%20al%200107.pdf }}</ref> inflammatory bowel disease<ref>{{cite journal | vauthors = Floer M, Götte M, Wild MK, Heidemann J, Gassar ES, Domschke W, Kiesel L, Luegering A, Kucharzik T | display-authors = 6 | title = Enoxaparin improves the course of dextran sodium sulfate-induced colitis in syndecan-1-deficient mice | journal = The American Journal of Pathology | volume = 176 | issue = 1 | pages = 146–157 | date = January 2010 | pmid = 20008145 | pmc = 2797877 | doi = 10.2353/ajpath.2010.080639 }}</ref> and experimental autoimmune encephalomyelitis<ref>{{cite journal | vauthors = Zhang X, Wu C, Song J, Götte M, Sorokin L | title = Syndecan-1, a cell surface proteoglycan, negatively regulates initial leukocyte recruitment to the brain across the choroid plexus in murine experimental autoimmune encephalomyelitis | journal = Journal of Immunology | volume = 191 | issue = 9 | pages = 4551–4561 | date = November 2013 | pmid = 24078687 | doi = 10.4049/jimmunol.1300931 | doi-access = free }}</ref> In experimental colitis-induced colon carcinoma, syndecan-1 deficiency promotes tumor growth in an IL-6 / STAT-signaling-dependent manner.<ref>{{cite journal | vauthors = Binder Gallimidi A, Nussbaum G, Hermano E, Weizman B, Meirovitz A, Vlodavsky I, Götte M, Elkin M | display-authors = 6 | title = Syndecan-1 deficiency promotes tumor growth in a murine model of colitis-induced colon carcinoma | journal = PLOS ONE | volume = 12 | issue = 3 | article-number = e0174343 | date = 2017 | pmid = 28350804 | pmc = 5369774 | doi = 10.1371/journal.pone.0174343 | doi-access = free | bibcode = 2017PLoSO..1274343B }}</ref>
==Clinical significance== Altered syndecan-1 expression has been detected in several different tumor types.<ref>{{cite journal | vauthors = Yip GW, Smollich M, Götte M | title = Therapeutic value of glycosaminoglycans in cancer | journal = Molecular Cancer Therapeutics | volume = 5 | issue = 9 | pages = 2139–2148 | date = September 2006 | pmid = 16985046 | doi = 10.1158/1535-7163.MCT-06-0082 | doi-access = free | url = https://aacr.figshare.com/articles/journal_contribution/Supplementary_Table_S1_from_Therapeutic_value_of_glycosaminoglycans_in_cancer/22484577/1/files/39936114.pdf }}</ref><ref>{{cite journal | vauthors = Stepp MA, Pal-Ghosh S, Tadvalkar G, Pajoohesh-Ganji A | title = Syndecan-1 and Its Expanding List of Contacts | journal = Advances in Wound Care | volume = 4 | issue = 4 | pages = 235–249 | date = April 2015 | pmid = 25945286 | pmc = 4397989 | doi = 10.1089/wound.2014.0555 }}</ref> In breast cancer, syndecan-1 is up regulated and contributes to the cancer stem cell phenotype, which is linked to increased resistance to chemotherapy and radiation therapy <ref>{{cite journal | vauthors = Hassan H, Greve B, Pavao MS, Kiesel L, Ibrahim SA, Götte M | title = Syndecan-1 modulates β-integrin-dependent and interleukin-6-dependent functions in breast cancer cell adhesion, migration, and resistance to irradiation | journal = The FEBS Journal | volume = 280 | issue = 10 | pages = 2216–2227 | date = May 2013 | pmid = 23289672 | doi = 10.1111/febs.12111 | s2cid = 19929711 | doi-access = }}</ref><ref>{{cite journal | vauthors = Ibrahim SA, Gadalla R, El-Ghonaimy EA, Samir O, Mohamed HT, Hassan H, Greve B, El-Shinawi M, Mohamed MM, Götte M | display-authors = 6 | title = Syndecan-1 is a novel molecular marker for triple negative inflammatory breast cancer and modulates the cancer stem cell phenotype via the IL-6/STAT3, Notch and EGFR signaling pathways | journal = Molecular Cancer | volume = 16 | issue = 1 | page = 57 | date = March 2017 | pmid = 28270211 | pmc = 5341174 | doi = 10.1186/s12943-017-0621-z | doi-access = free }}</ref><ref>{{cite journal | vauthors = Götte M, Kersting C, Ruggiero M, Tio J, Tulusan AH, Kiesel L, Wülfing P | title = Predictive value of syndecan-1 expression for the response to neoadjuvant chemotherapy of primary breast cancer | journal = Anticancer Research | volume = 26 | issue = 1B | pages = 621–627 | date = 2006 | pmid = 16739330 | url = http://ar.iiarjournals.org/content/26/1B/621.long }}</ref>
It is a specific antigen on multiple myeloma cells.<ref name=ASH2013>[http://www.myelomabeacon.com/resources/mtgs/ash2013/abs/758/ Indatuximab Ravtansine (BT062) In Combination With Lenalidomide and Low-Dose Dexamethasone In Patients With Relapsed and/Or Refractory Multiple Myeloma: Clinical Activity In Len/Dex-Refractory Patients]</ref> Indatuximab ravtansine targets this protein.
== Application == It is a useful marker for plasma cells,<ref name="pmid18770841">{{cite book | vauthors = Rawstron AC | chapter = Chapter 6: Immunophenotyping of plasma cells | title = Current Protocols in Cytometry | issue = 1 | pages = Unit 6.23 | date = May 2006 | volume = Chapter 6 | pmid = 18770841 | doi = 10.1002/0471142956.cy0623s36 | isbn = 0-471-14295-6 | s2cid = 19511070 }}</ref> but only if the cells tested are already known to be derived from blood.<ref name="pmid14983940">{{cite journal | vauthors = O'Connell FP, Pinkus JL, Pinkus GS | title = CD138 (syndecan-1), a plasma cell marker immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms | journal = American Journal of Clinical Pathology | volume = 121 | issue = 2 | pages = 254–263 | date = February 2004 | pmid = 14983940 | doi = 10.1309/617D-WB5G-NFWX-HW4L | doi-access = free | author3-link = Geraldine Pinkus }}{{Dead link|date=June 2018 |bot=InternetArchiveBot |fix-attempted=no }}</ref> For plasma cells, it usually stains intensely membranous, with or without associated diffuse weak cytoplasmic and/or Golgi staining.<ref name="pmid17714757">{{cite journal | vauthors = Al-Quran SZ, Yang L, Magill JM, Braylan RC, Douglas-Nikitin VK | title = Assessment of bone marrow plasma cell infiltrates in multiple myeloma: the added value of CD138 immunohistochemistry | journal = Human Pathology | volume = 38 | issue = 12 | pages = 1779–1787 | date = December 2007 | pmid = 17714757 | pmc = 3419754 | doi = 10.1016/j.humpath.2007.04.010 }}</ref> Few cases show cytoplasmic granular staining, with or without associated Golgi staining.<ref name="pmid17714757"/>
== References == {{reflist}}
== Further reading == {{refbegin | 2}} * {{cite book | vauthors = David G | title = Heparin and Related Polysaccharides | chapter = Structural and Functional Diversity of the Heparan Sulfate Proteoglycans | series = Advances in Experimental Medicine and Biology | volume = 313 | pages = 69–78 | year = 1992 | pmid = 1442271 | doi = 10.1007/978-1-4899-2444-5_7 | isbn = 978-1-4899-2446-9 }} * {{cite book | vauthors = Jaakkola P, Jalkanen M | title = Transcriptional regulation of Syndecan-1 expression by growth factors | volume = 63 | pages = 109–38 | year = 1999 | pmid = 10506830 | doi = 10.1016/S0079-6603(08)60721-7 | isbn = 978-0-12-540063-3 | series = Progress in Nucleic Acid Research and Molecular Biology }} * {{cite journal | vauthors = Wijdenes J, Dore JM, Clement C, Vermot-Desroches C | title = CD138 | journal = Journal of Biological Regulators and Homeostatic Agents | volume = 16 | issue = 2 | pages = 152–155 | year = 2003 | pmid = 12144130 }} * {{cite journal | vauthors = Lories V, Cassiman JJ, Van den Berghe H, David G | title = Differential expression of cell surface heparan sulfate proteoglycans in human mammary epithelial cells and lung fibroblasts | journal = The Journal of Biological Chemistry | volume = 267 | issue = 2 | pages = 1116–1122 | date = January 1992 | pmid = 1339431 | doi = 10.1016/S0021-9258(18)48404-9 | doi-access = free }} * {{cite journal | vauthors = Vainio S, Jalkanen M, Bernfield M, Saxén L | title = Transient expression of syndecan in mesenchymal cell aggregates of the embryonic kidney | journal = Developmental Biology | volume = 152 | issue = 2 | pages = 221–232 | date = August 1992 | pmid = 1644217 | doi = 10.1016/0012-1606(92)90130-9 }} * {{cite journal | vauthors = Kiefer MC, Ishihara M, Swiedler SJ, Crawford K, Stephans JC, Barr PJ | title = The molecular biology of heparan sulfate fibroblast growth factor receptors | journal = Annals of the New York Academy of Sciences | volume = 638 | pages = 167–176 | year = 1992 | pmid = 1664683 | doi = 10.1111/j.1749-6632.1991.tb49027.x | s2cid = 29216939 }} * {{cite journal | vauthors = Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J | title = Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2 | journal = Somatic Cell and Molecular Genetics | volume = 16 | issue = 5 | pages = 501–505 | date = September 1990 | pmid = 2173154 | doi = 10.1007/BF01233200 | s2cid = 43270934 }} * {{cite journal | vauthors = Mali M, Jaakkola P, Arvilommi AM, Jalkanen M | title = Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans | journal = The Journal of Biological Chemistry | volume = 265 | issue = 12 | pages = 6884–6889 | date = April 1990 | pmid = 2324102 | doi = 10.1016/S0021-9258(19)39232-4 | doi-access = free }} * {{cite journal | vauthors = Sanderson RD, Lalor P, Bernfield M | title = B lymphocytes express and lose syndecan at specific stages of differentiation | journal = Cell Regulation | volume = 1 | issue = 1 | pages = 27–35 | date = November 1989 | pmid = 2519615 | pmc = 361422 | doi = 10.1091/mbc.1.1.27 }} * {{cite journal | vauthors = Asundi VK, Carey DJ | title = Self-association of N-syndecan (syndecan-3) core protein is mediated by a novel structural motif in the transmembrane domain and ectodomain flanking region | journal = The Journal of Biological Chemistry | volume = 270 | issue = 44 | pages = 26404–26410 | date = November 1995 | pmid = 7592855 | doi = 10.1074/jbc.270.44.26404 | doi-access =free }} * {{cite journal | vauthors = Zhang L, David G, Esko JD | title = Repetitive Ser-Gly sequences enhance heparan sulfate assembly in proteoglycans | journal = The Journal of Biological Chemistry | volume = 270 | issue = 45 | pages = 27127–27135 | date = November 1995 | pmid = 7592967 | doi = 10.1074/jbc.270.45.27127 | doi-access = free }} * {{cite journal | vauthors = Barillari G, Gendelman R, Gallo RC, Ensoli B | title = The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the RGD amino acid sequence | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 17 | pages = 7941–7945 | date = September 1993 | pmid = 7690138 | pmc = 47263 | doi = 10.1073/pnas.90.17.7941 | doi-access = free | bibcode = 1993PNAS...90.7941B }} * {{cite journal | vauthors = Spring J, Goldberger OA, Jenkins NA, Gilbert DJ, Copeland NG, Bernfield M | title = Mapping of the syndecan genes in the mouse: linkage with members of the myc gene family | journal = Genomics | volume = 21 | issue = 3 | pages = 597–601 | date = June 1994 | pmid = 7959737 | doi = 10.1006/geno.1994.1319 }} * {{cite journal | vauthors = Sneed TB, Stanley DJ, Young LA, Sanderson RD | title = Interleukin-6 regulates expression of the syndecan-1 proteoglycan on B lymphoid cells | journal = Cellular Immunology | volume = 153 | issue = 2 | pages = 456–467 | date = February 1994 | pmid = 8118875 | doi = 10.1006/cimm.1994.1042 }} * {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–174 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }} * {{cite journal | vauthors = Kokenyesi R, Bernfield M | title = Core protein structure and sequence determine the site and presence of heparan sulfate and chondroitin sulfate on syndecan-1 | journal = The Journal of Biological Chemistry | volume = 269 | issue = 16 | pages = 12304–12309 | date = April 1994 | pmid = 8163535 | doi = 10.1016/S0021-9258(17)32716-3 | doi-access = free }} * {{cite journal | vauthors = Albini A, Benelli R, Presta M, Rusnati M, Ziche M, Rubartelli A, Paglialunga G, Bussolino F, Noonan D | display-authors = 6 | title = HIV-tat protein is a heparin-binding angiogenic growth factor | journal = Oncogene | volume = 12 | issue = 2 | pages = 289–297 | date = January 1996 | pmid = 8570206 }} * {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = September 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 | doi-access = free }} * {{cite journal | vauthors = Kaukonen J, Alanen-Kurki L, Jalkanen M, Palotie A | title = The mapping and visual ordering of the human syndecan-1 and N-myc genes near the telomeric region of chromosome 2p | journal = Human Genetics | volume = 99 | issue = 3 | pages = 295–297 | date = March 1997 | pmid = 9050911 | doi = 10.1007/s004390050360 | s2cid = 30155082 }} {{refend}}
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{{Clusters of differentiation}} {{Clusters of differentiation by lineage}} {{Proteoglycans}}
Category:Proteoglycans