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Syndecan 1 is a protein which in humans is encoded by the ''SDC1'' gene. The protein is a transmembrane (type I) heparan sulfate
proteoglycan Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to whic ...
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 proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation re ...
, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Syndecan-1 is a sponge for growth factors and chemokines, 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 cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B lymphocytes and secrete large quantities of proteins called antibodies in response to being presented specific substan ...
s.


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. The extracellular domain can be cleaved (shed) from the cell surface at a juxtamembrane site, converting the membrane-bound proteoglycan into a paracrine effector molecule with roles in wound repair and invasive growth of cancer cells. An exception is the prosecretory mitogen lacritin that binds syndecan-1 only after heparanase modification.ubMed - indexed for MEDLINE> 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. 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.ubMed - 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.ubMed - 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.


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 Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
and dendritic cells) to the inflamed endothelium. This increase results in higher inflammatory responses and tissue damage in experimental models of contact dermatitis, inflammation of the kidney, myocardial infarction,
inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...
and experimental autoimmune encephalomyelitis In experimental colitis-induced colon carcinoma, syndecan-1 deficiency promotes tumor growth in an IL-6 / STAT-signaling-dependent manner.


Clinical significance

Altered syndecan-1 expression has been detected in several different tumor types. In breast cancer, syndecan-1 is up regulated and contributes to the
cancer stem cell Cancer stem cells (CSCs) are cancer cells (found within tumors or hematological cancers) that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. ...
phenotype, which is linked to increased resistance to chemotherapy and radiation therapy It is a specific antigen on
multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, an ...
cells.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
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Indatuximab ravtansine Indatuximab ravtansine (BT062) is an immunomodulator and antineoplastic antibody-drug conjugate. It is the anti-CD138 chimerized MAb (nBT062) linked to the maytansinoid DM4. It is being investigated as part of a treatment for multiple myeloma ...
targets this protein.


Application

It is a useful marker for
plasma cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B lymphocytes and secrete large quantities of proteins called antibodies in response to being presented specific substan ...
s, but only if the cells tested are already known to be derived from blood. For plasma cells, it usually stains intensely membranous, with or without associated diffuse weak cytoplasmic and/or Golgi staining. Few cases show cytoplasmic granular staining, with or without associated Golgi staining.


References


Further reading

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