FIGURE 6.

Working model for shed syndecan-1 translocation and functions in the nucleus. 1, aggressive myeloma cells shed high levels of SDC1 and secrete heparan sulfate-binding factors (e.g. growth factors such as HGF) into the tumor microenvironment. 2, sSDC1 forms a complex with heparan sulfate-binding factors; the complex binds to the cell surface and enters potentially via an endocytic receptor-mediated pathway. 3, sSDC1·heparan sulfate-binding protein complex is transported to the nucleus. 4, in the nucleus, shed syndecan-1 binds p300 and down-regulates histone acetyltransferase activity and histone acetylation. This mechanism for transport of sSDC1 to the nucleus may not be exclusive to sSDC1, but it may also function to transport free heparan sulfate chains or heparanase-generated heparan sulfate fragments to the nucleus.