Hyaluronan oligosaccharides and tumor progression

Abstract

Accumulating evidence indicates that hyaluronan (HA), a high molecular weight polymer that exists as a component of the extracellular matrix, is critically involved in tumor development and progression. HA synthesis is upregulated in various malignant tumors, resulting in the enhancement of tumor cell adhesion and migration, and mediation of signaling pathways. Furthermore, during tumor progression, HA that has been degraded into oligosaccharides has been reported in the urine, blood or tumor tissue specimens of the patients with tumors. HA oligosaccharides are involved in functions such as angiogenesis, cell migration, and proliferation, and these functions are distinct from those of large HA polymers. We recently found that HA oligosaccharides of a certain size range induce proteolytic cleavage of CD44 from tumor cells (CD44 cleavage) and promote tumor cell migration in a CD44-dependent manner. Our results suggest that HA oligosaccharides serve as a physiological inducer of CD44 cleavage in vivo and reinforce the idea that they play an important role in tumor invasion. In this review, we will discuss the biological functions of HA oligosaccharides and their possible role in tumor development and progression.