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2014 ; 123
(ä): 191-209
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Hyaluronan regulation of endothelial barrier function in cancer
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Singleton PA
Adv Cancer Res
2014[]; 123
(ä): 191-209
PMID25081530
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Vascular integrity or the maintenance of blood vessel continuity is a fundamental
process regulated by endothelial cell-cell junctions. Defects in endothelial
barrier function are an initiating factor in several disease processes including
tumor angiogenesis and metastasis. The glycosaminoglycan, hyaluronan (HA),
maintains vascular integrity through specific mechanisms including HA-binding
protein signaling in caveolin-enriched microdomains, a subset of lipid rafts.
Certain disease states, including cancer, increase enzymatic hyaluronidase
activity and reactive oxygen species generation, which break down high molecular
weight HA (HMW-HA) to low molecular weight fragments (LMW-HA). LMW-HA can
activate specific HA-binding proteins during tumor progression to promote
disruption of endothelial cell-cell contacts. In contrast, exogenous
administration of HMW-HA promotes enhancement of vascular integrity. This review
focuses on the roles of HA in regulating angiogenic and metastatic processes
based on its size and the HA-binding proteins present. Further, potential
therapeutic applications of HMW-HA in treating cancer are discussed.
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