Martin Götte
University of Munster, Germany
Title: The heparan sulfate proteoglycan Syndecan-1 and heparanase are novel regulators of cancer stem cell function and therapeutic resistance
Biography
Biography: Martin Götte
Abstract
The heparan sulfate proteoglycan Syndecan-1 binds cytokines, morphogens and extracellular matrix
components, regulating cancer stem cell properties and invasiveness. Syndecan-1 is modulated by
the heparan sulfate-degrading enzyme heparanase, but the underlying regulatory mechanisms are
only poorly understood (1). In colon cancer pathogenesis, complex changes occur in the expression
pattern of Syndecan-1 and heparanase during progression from well-differentiated to
undifferentiated tumors. Loss of Syndecan-1 and increased expression of heparanase are associated
with a change in phenotypic plasticity and an increase in invasiveness, metastasis and
dedifferentiation. Here we investigated the regulatory and functional interplay of Syndecan-1 and
heparanase employing siRNA-mediated silencing and plasmid-based overexpression approaches in
human colon cancer cell lines and in a xenograft model (2,3). Sdc-1 small-interfering RNA knockdown
in the human colon cancer cell lines Caco2 and HT-29 resulted in an increased side population (SP),
enhanced aldehyde dehydrogenase 1 activity, and higher expression of CD133,CD133, LGR5, EPCAM,
NANOG, SRY (sex-determining region Y)-box 2, KLF2, and TCF4/TCF7L2.