Soluble Syndecan-1: Does This Biomarker Address a Seemingly Insoluble Problem in Inflammatory Bowel Disease?

Syndecans are a major class of cell surface heparan sulfate proteoglycan (HSPG) that help maintain physiological homeostasis. Changes in expression and function of these molecules are associated with and contribute to many pathophysiological conditions including malignancies and inflammation. Syndecans are composed of a core protein comprised of an ectodomain, a transmembrane domain, and a conserved cytoplasmic domain, with three or more structurally diverse heparan sulfate chains. Four individual syndecans are expressed in a highly regulated tissue-, cell-, and development-specific manner. As part of normal cell HSPG turnover, the intact ectodomain is shed from the cell surface, rendering HSPG soluble. Membrane-bound and soluble HSPG can act either as paracrine or autocrine effectors or as negative modulators of cellular signaling events. Syndecan shedding occurs by highly regulated cleavage mechanisms in response to specific developmental and homeostatic signals, but also in response to pathophysiological signals such as inflammatory cytokines and chemokines, as illustrated in Fig. 1 . Of the four identified syndecans, syndecan-1 is predominantly expressed by plasma cells and mucosal epithelial cells, such as intestinal epithelial cells. Syndecan expression and shedding is highly modulated in inflammation-associated disease states, such as Crohn’s disease or ulcerative colitis.