Syndecans in cancer: A review of function, expression, prognostic value, and therapeutic significance.

While our understanding of tumors and how to treat them has advanced significantly since the days of Aminopterin and the radical mastectomy, cancer remains among the leading causes of death worldwide. Despite innumerable advancements in medical technology the non-static and highly heterogeneous nature of a tumor can make characterization and treatment exceedingly difficult. Because of this complexity, the identification of new cellular constituents that can be used for diagnostic, prognostic, and therapeutic purposes is crucial in improving patient outcomes worldwide. Growing evidence has demonstrated that among the myriad of changes seen in cancer cells, the Syndecan family of proteins has been observed to undergo drastic alterations in expression. Syndecans are transmembrane heparan sulfate proteoglycans that are responsible for cell signaling, proliferation, and adhesion, and many studies have shed light on their unique involvement in both tumor progression and suppression. This review seeks to discuss Syndecan expression levels in various cancers, whether they make reliable biomarkers for detection and prognosis, and whether they may be viable targets for future cancer therapies. The conclusions drawn from the literature reviewed in this article indicate that changes in expression of Syndecan protein can have profound effects on tumor size, metastatic capability, and overall patient survival rate. Further, while data regarding the therapeutic targeting of Syndecan proteins is sparse, the available literature does demonstrate promise for their use in cancer treatment going forward.

Identification of biomarkers indicative of functional skeletal stem cells.

OBJECTIVES: Skeletal stem cells (SSCs) are characterized by expression of cell surface biomarkers and their ability to differentiate into bone, cartilage and fat. However, the current biomarkers used to identify these cell populations are not cell-type-specific or indicative of the differentiation status of these cells and are therefore unreliable. Our objective was to identify alternative cell surface biomarkers and transcription factors shared between SSCs isolated from the bone marrow (BM) and those derived from pluripotent stem cells (PSC). MATERIALS AND METHODS: Human PSCs were induced into SSCs. FACS and qRT-PCR were used to determine differences in expression of cell surface biomarkers and transcription factors between SSCs derived from PSCs and isolated from BM, in differentiating cells, in cells from early and late passage, and in fibroblasts. RESULTS: A significant reduction in proliferation and capacity of SSCs to differentiate into adipocytes and osteoblasts was observed after 3 passages. Protein and mRNA analysis indicated that commonly used biomarkers remain highly expressed in cells that lost capacity for differentiation. However, integrin α6 (CD49f) and transcription factors GATA6, PRDM16, SIM2 and SOX11 were significantly upregulated in SSCs compared to fibroblasts. In early stages of adipogenic and osteogenic differentiation, the expression of CD49f, GATA6 and SIM2 was reduced in later passage cells, which have limited proliferation and differentiation capabilities. CONCLUSIONS: Our results suggest that CD49f and transcription factors GATA6 and SIM2 identify functional SSCs.

Integrin α6 (CD49f), The Microenvironment and Cancer Stem Cells.

Cancer is a highly prevalent and potentially terminal disease that affects millions of individuals worldwide. Here, we review the literature exploring the intricacies of stem cells bearing tumorigenic characteristics and collect evidence demonstrating the importance of integrin α6 (ITGA6, also known as CD49f) in cancer stem cell (CSC) activity. ITGA6 is commonly used to identify CSC populations in various tissues and plays an important role sustaining the self-renewal of CSCs by interconnecting them with the tumorigenic microenvironment.