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Syndecan-1: a dynamic regulator of the myeloma microenvironment

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Abstract

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.

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Abbreviations

EGF:

Epidermal growth factor

FGF:

Fibroblast growth factor

FGFR:

Fibroblast growth factor receptor

HGF:

Hepatocyte growth factor

MMP:

Matrix metalloproteinase

OPG:

Osteoprotegerin

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptor

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Acknowledgements

This work was supported by NIH CA103054 and CA55819 to RDS. The authors apologize for the inability, due to space limitations, to reference all studies relevant to this review.

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Correspondence to Ralph D. Sanderson.

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Sanderson, R.D., Yang, Y. Syndecan-1: a dynamic regulator of the myeloma microenvironment. Clin Exp Metastasis 25, 149–159 (2008). https://doi.org/10.1007/s10585-007-9125-3

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  • DOI: https://doi.org/10.1007/s10585-007-9125-3

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