Impact of the hyaluronan-rich tumor microenvironment on cancer initiation and progression.

Hyaluronan acts as a microenvironmental stimulus that can influence the malignant phenotype of cancer cells. During cancer progression, hyaluronan assembles an extracellular matrix that is favorable for both the motility and proliferation of cancer cells and the recruitment of inflammatory and bone marrow-derived progenitor cells. The varied roles of this polysaccharide are regulated via multiple mechanisms involving biosynthesis, degradation, binding with other extracellular molecules, and activation of signaling pathways. Recent animal studies have provided evidence that aberrant biosynthesis of hyaluronan accelerates tumor growth through a diverse repertoire of host-tumor interactions, such as stromal cell recruitment, angiogenesis, lymphangiogenesis, and inflammation. Hyaluronan in the tumor microenvironment thus significantly impacts cancer initiation and progression via stroma-cancer cell interactions.