Syndecan-1: a dynamic regulator of the myeloma microenvironment.
Emerging data in myeloma and other cancers indicates that heparan sulfate proteoglycans promote tumor progression by enhancing their growth and metastasis. By acting as key regulators of cell signaling via their interactions with multiple growth and angiogenic factors, heparan sulfates mediate a shift in the microenvironment that supports the tumor as an 'organ' and promotes an aggressive tumor phenotype. In addition, enzymatic remodeling of heparan sulfate proteoglycans provides a mechanism for rapid, localized and dynamic modulation of proteoglycan function thereby tightly regulating activities within the tumor microenvironment. New data from animal models demonstrates that heparan sulfate or the enzymes that regulate heparan sulfate are viable targets for cancer therapy. This strategy of targeting heparan sulfate may be particularly effective for attacking cancers like myeloma where extensive genetic chaos renders them unlikely to respond well to agents that target a single signaling pathway.
Sanderson
Ralph D
RD
Department of Pathology, Division of Cellular and Molecular Pathology, University of Alabama at Birmingham, 814 Shelby Building, 1530 Third Avenue South, Birmingham, AL 35294-2182, USA. Sanderson@uab.edu
Yang
Yang
Y
D000818:Animals; D049109:Cell Proliferation; D005966:Glucuronidase / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D015398:Signal Transduction; D013429:Sulfatases / Q000378:metabolism; D053668:Syndecan-1 / Q000502:physiology*; D000099175:Heparanase
D005966:Glucuronidase; D006497:Heparan Sulfate; D013429:Sulfatases; D053668:Syndecan-1; D000099175:Heparanase