Role of Syndecan-1 in Cancer Stem Cells

Syndecan-1 (CD138) is a cell surface heparan sulfate proteoglycan that is frequently misexpressed in cancer. Under physiological and pathological conditions, it is involved in the regulation of diverse processes, such as leukocyte recruitment, wound repair, angiogenesis, exosome formation, and epithelial-to-mesenchymal transition. Apart from its role as an adhesion molecule and a modulator of proteolysis, Syndecan-1 has a pivotal function as a co-receptor for multiple signal transduction pathways, including Wnt, hedgehog, FGF, and NF-kB/IL-6/JAK/STAT3 signaling. Notably, the activity of these pathways plays an important role in determining the functional state of cancer stem cells. This cell population shares several properties with stem cells, and has been linked to cancer recurrence due to its property of increased resistance to chemo- and radiation therapies. In this chapter, we summarize the current knowledge on the role of Syndecan-1 in cancer stem cell function. Due to its simultaneous involvement as an enhancer of multiple stemness-associated signaling pathways, Syndecan-1 emerges as an attractive target for novel therapeutic approaches, which could be utilized to overcome recurrence after an otherwise successful therapy.