The syndecan-1 core protein consists of an extracellular domain which can be substituted with heparan sulfate andchondroitin sulfateglycosaminoglycan chains, a highly conserved transmembrane domain, and a highly conserved cytoplasmic domain, which contains two constant regions that are separated by a variable region.[8] The extracellular domain can be cleaved (shed) from the cell surface at a juxtamembrane site,[9] converting the membrane-bound proteoglycan into a paracrine effector molecule with roles in wound repair[10] and invasive growth of cancer cells.[11]
An exception is the prosecretory mitogenlacritin that binds syndecan-1 only after heparanase modification.[12][13] Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelialheparanase (HPSE) cleaves off heparan sulfate to expose a binding site in the N-terminal region of syndecan-1's core protein.[12] 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.[13] 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.[13]
While severaltranscript 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.[14]
Altered syndecan-1 expression has been detected in several different tumor types.[23][24] Inbreast cancer, syndecan-1 is up regulated and contributes to thecancer stem cell phenotype, which is linked to increased resistance tochemotherapy and radiation therapy[25][26][27]
It is a useful marker forplasma cells,[29] but only if the cells tested are already known to be derived from blood.[30] For plasma cells, it usually stains intensely membranous, with or without associated diffuse weak cytoplasmic and/or Golgi staining.[31] Few cases show cytoplasmic granular staining, with or without associated Golgi staining.[31]
^Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J (September 1990). "Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2".Somatic Cell and Molecular Genetics.16 (5):501–505.doi:10.1007/BF01233200.PMID2173154.S2CID43270934.
^Bernfield M, Götte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M (1999). "Functions of cell surface heparan sulfate proteoglycans".Annual Review of Biochemistry.68:729–777.doi:10.1146/annurev.biochem.68.1.729.PMID10872465.
^Averbeck M, Kuhn S, Bühligen J, Götte M, Simon JC, Polte T (November 2017). "Syndecan-1 regulates dendritic cell migration in cutaneous hypersensitivity to haptens".Experimental Dermatology.26 (11):1060–1067.doi:10.1111/exd.13374.PMID28453867.S2CID38757296.
^Hassan H, Greve B, Pavao MS, Kiesel L, Ibrahim SA, Götte M (May 2013). "Syndecan-1 modulates β-integrin-dependent and interleukin-6-dependent functions in breast cancer cell adhesion, migration, and resistance to irradiation".The FEBS Journal.280 (10):2216–2227.doi:10.1111/febs.12111.PMID23289672.S2CID19929711.
David G (1992). "Structural and Functional Diversity of the Heparan Sulfate Proteoglycans".Heparin and Related Polysaccharides. Advances in Experimental Medicine and Biology. Vol. 313. pp. 69–78.doi:10.1007/978-1-4899-2444-5_7.ISBN978-1-4899-2446-9.PMID1442271.
Vainio S, Jalkanen M, Bernfield M, Saxén L (August 1992). "Transient expression of syndecan in mesenchymal cell aggregates of the embryonic kidney".Developmental Biology.152 (2):221–232.doi:10.1016/0012-1606(92)90130-9.PMID1644217.
Kiefer MC, Ishihara M, Swiedler SJ, Crawford K, Stephans JC, Barr PJ (1992). "The molecular biology of heparan sulfate fibroblast growth factor receptors".Annals of the New York Academy of Sciences.638:167–176.doi:10.1111/j.1749-6632.1991.tb49027.x.PMID1664683.S2CID29216939.
Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J (September 1990). "Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2".Somatic Cell and Molecular Genetics.16 (5):501–505.doi:10.1007/BF01233200.PMID2173154.S2CID43270934.
Spring J, Goldberger OA, Jenkins NA, Gilbert DJ, Copeland NG, Bernfield M (June 1994). "Mapping of the syndecan genes in the mouse: linkage with members of the myc gene family".Genomics.21 (3):597–601.doi:10.1006/geno.1994.1319.PMID7959737.
Sneed TB, Stanley DJ, Young LA, Sanderson RD (February 1994). "Interleukin-6 regulates expression of the syndecan-1 proteoglycan on B lymphoid cells".Cellular Immunology.153 (2):456–467.doi:10.1006/cimm.1994.1042.PMID8118875.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides".Gene.138 (1–2):171–174.doi:10.1016/0378-1119(94)90802-8.PMID8125298.
Albini A, Benelli R, Presta M, Rusnati M, Ziche M, Rubartelli A, et al. (January 1996). "HIV-tat protein is a heparin-binding angiogenic growth factor".Oncogene.12 (2):289–297.PMID8570206.
Kaukonen J, Alanen-Kurki L, Jalkanen M, Palotie A (March 1997). "The mapping and visual ordering of the human syndecan-1 and N-myc genes near the telomeric region of chromosome 2p".Human Genetics.99 (3):295–297.doi:10.1007/s004390050360.PMID9050911.S2CID30155082.
