Sclerostin, the protein product of the SOST gene, is a potent inhibitor of bone formation. Sclerostin protein is widely expressed at low levels with highest levels in bone, cartilage, kidney, liver, bone marrow and primary osteeoblasts differentiated for 21 days, and was originally identified as an important regulator of bone remodeling, homeostasis, and links bone resorption and bone apposition. Recent studies have revealed that Sclerostin protein inhibits the bone growth probably by binding to the extracellular domain of the Wnt coreceptors LRP5 and LRP6 and disrupting Wnt-induced Frizzled-LRP complex formation.
Stromal derived factors (SDFs) are a loosely defined group of molecules that are generated by stromal cells. Two of the stromal derived factors, SDF-1 and SDF-4 belong to the chemokine family. Other SDFs, such as SDF-2 and SDF-5 are not well defined and their biological functions are less known. SDF-2 is first isolated from themousestromal cell lineST2 as asecretory protein. The amino acid sequence deduced from themurineclone and thehumanhomologare conserved more than 92 %, and the aa sequence of SDF-2 shows similarity to those ofyeastdolichyl phosphate-D-mannose, protein mannosyltransferases. SDF-1 and its receptor are strongly indicated in the progression of various cancers including breast cancer. SDF-2, SDF2-L1, SDF-4, and SDF-5 are ubiquitously expressed in various cancer cell lines and SDF-2, SDF-4 and SDF-5 are expressed in mammary tissues. These SDFs have prognostic value and warrant further investigation in their biological functions and clinical value.
SECTM1A (secreted and transmembrane 1A), is 192 amino acid (aa) protein, appears to share structural and functional characteristics with other SECTM1 proteins. Human SECTM1 can be found either found as an approximately 27 kDa intracellular type I transmembrane protein that shows a perinuclear, Golgi like staining pattern, or as a 20 kDa soluble, secreted form, and is produced by some myeloid cells and by thymic epithelia and fibroblasts. Stimulation with IFN gamma is often necessary to detect human SECTM1 expression, and it is thought to be an interferon early response gene. Mouse SECTM1A cDNA encodes a signal sequence, an extracellular domain with four potential N linked glycosylation sites, a transmembrane sequence, and a very short (approximately 6 aa) cytoplasmic sequence. SECTM1 proteins from human and mouse show species specific binding of CD7 and co stimulation of T cells, including enhancement of CD3 induced proliferation.
Selenoprotein P (SeP) is an extracellular, monomeric glycoprotein containing up to 10 selenocysteine residues in the polypeptide chain. It is ubiquitously expressed in mammalian tissues, and in human plasma it accounts for at least 40% of the total selenium concentration. SeP binds to heparin and cell membranes, and is associated with endothelial cells. SeP in human plasma protects against peroxynitrite-mediated oxidation and reduces phospholipid hydroperoxide in vitro, in accordance with the presumption that it has a function as an extracellular oxidant defense. Immunochemical assays have demonstrated that its concentration in plasma varies much with selenium intake, but other factors also have an influence.
E-selectin, also known as endothelial leukocyte adhesion molecule-1 (ELAM-1) and CD62E, is an inducible adhesion molecule that is expressed on the surfaces of stimulated vascular endothelial cells and is sometimes involved in cancer cell metastasis. E-selectin exhibits a complex mosaic structure consisting of a large extracellular region comprised of a lectin domain, an EGF-like domain, and a short consensus repeat (SCR) domain, followed by a transmembrane region and a relatively short (32 aa) cytoplasmic tail. As a member of the LEC-CAM or selectin family, E-selectin recognises and binds to sialylated carbohydrates including members of the Lewis X and Lewis A families found on monocytes, granulocytes, and T-lymphocytes. E-selectin supports rolling and stable arrest of leukocytes on activated vascular endothelium, and furthermore, it was indicated that it can also transduce an activating stimulus via the MAPK cascade into the endothelial cell during leukocyte adhesion. E-selectin regulates adhesive interactions between certain blood cells and endothelium. The soluble form of E selectin (sE-selectin) is a marker of endothelial activation, and has a potential role in the pathogenesis of cardiovascular disease as raised levels have been found in hypertension, diabetes and hyperlipidemia, although its association in established atherosclerosis disease and its value as a prognostic factor is more controversial. soluble E-selectin is inversely associated with an the muscular component of the left ventricle, thereby suggesting that the lack of such a reparative factor may be associated with an cardiac remodeling in end-stage renal disease (ESRD) patients. Besides, this adhesion molecule appears to be involved in the pathogenesis of atherosclerosis.
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