Hyaluronan: molecular size-dependent signaling and biological functions in inflammation and cancer.

Hyaluronan (HA) is a linear non-sulfated glycosaminoglycan of the extracellular matrix that plays a pivotal role in a variety of biological processes. High molecular size HA exhibit different biological properties than oligomers and low molecular size HA. Depending on their molecular size, HA fragments can influence cellular behavior in a different mode of action. This phenomenon is attributed to the different manner of interaction with the HA receptors, especially CD44 and RHAMM. Both receptors can trigger signaling cascades that regulate cell functional properties, such as proliferation and migration, angiogenesis and wound healing. HA fragments are able to enhance or attenuate the HA receptors-mediated signaling pathways, as they compete with the endogenous HA for binding to the receptors. The modulation of these pathways could be crucial for the development of pathological conditions, such as inflammation and cancer. The primary goal of this review is to critically present the importance of HA molecular size on cellular signalling, functional cell properties and morphology in normal and pathological conditions, including inflammation and cancer. A deeper understanding of these mechanisms could contribute on the development of therapeutic strategies. This article is protected by copyright. All rights reserved.