Syndecan-1 (CD138), Carcinomas and EMT

Abstract

Cell surface proteoglycans are known to be important regulators of many aspects of cell behavior. The principle family of transmembrane proteoglycans is the syndecans, of which there are four in mammals. Syndecan-1 is mostly restricted to epithelia, and bears heparan sulfate chains that are capable of interacting with a large array of polypeptides, including extracellular matrix components and potent mediators of proliferation, adhesion and migration. For this reason, it has been studied extensively with respect to carcinomas and tumor progression. Frequently, but not always, syndecan-1 levels decrease as tumor grade, stage and invasiveness and dedifferentiation increase. This parallels experiments that show depletion of syndecan-1 can be accompanied by loss of cadherin-mediated adhesion. However, in some tumors, levels of syndecan-1 increase, but the characterization of its distribution is relevant. There can be loss of membrane staining, but acquisition of cytoplasmic and/or nuclear staining that is abnormal. Moreover, the appearance of syndecan-1 in the tumor stroma, either associated with its cellular component or the collagenous matrix, is nearly always a sign of poor prognosis. Given its relevance to myeloma progression, syndecan-1-directed antibody—toxin conjugates are being tested in clinical and preclinical trials, and may have future relevance to some carcinomas.

Syndecan Family Gene and Protein Expression and Their Prognostic Values for Prostate Cancer

“…The cytosolic conserved C1 domain is involved in interacting with the actin filaments via binding to ezrin, radixin, and moesin proteins. In its turn, the C2 domain interacts with synectin, syntenin, and calcium-calmodulin-associated serine/threonine kinase [16,18,19]. Readers are referred to references [19,20] for detailed reviews on syndecans.…”

“…The syndecans play an important role in the progression and prognosis of many types of cancer [21][22][23]. SDC1 is the best-characterized member of the SDC family and is expressed in all types of epithelial cells [18,24,25]. Loss of SDC1 is associated with tumor progression and poor prognosis in a variety of cancers [26][27][28].…”

The Tissue Architecture of Oral Squamous Cell Carcinoma Visualized by Staining Patterns of Wheat Germ Agglutinin and Structural Proteins Using Confocal Microscopy

“…We detected prominent cytoplasmic β-actin staining in cells from tumor clusters as well, associated with elongated cell morphologies, and a shift from cortical to cytoplasmic actin is another feature of EMT [ 23 ]. Loss of polygonal cell morphologies was also observed in tumor cells with strong cytoplasmic syndecan-1 expression, and cytoplasmic redistribution of syndecan has been linked with increased tumor invasiveness [ 24 ]. Our results showing co-expression of vimentin and pan-cytokeratin and co-expression of vimentin and Ki-67 in tumor clusters are also consistent with the acquisition of mesenchymal properties, while still retaining epithelial characteristics and the proliferative activity found in OSCC invasive regions with high numbers of tumor clusters [ 25 ].…”

Integrin α11β1 in tumor fibrosis: more than just another cancer-associated fibroblast biomarker?

“…The authors suggest that stromal-derived syndecan-2 influences tumor progression by modulating TGF-β signaling in the tumor microenvironment (Loftus et al 2021 ). Stromal syndecan-1 expression in most tumor types is a poor prognostic factor (Couchman 2021 ). However, the origin of stromal syndecan-1 in carcinomas is mostly unknown and may in some studies been produced by mesenchymal cells or shed from epithelial cells.…”