Hyaluronan: Cancer and Cancer Metastasis

Abstract

Hyaluronan (HA), a major component of the extracellular matrix, provides a favorable microenvironment for cell growth, proliferation, migration, and metastasis in most malignant tumors. This polysaccharide promotes these cellular events through the remodeling of the tumor microenvironment, the recruitment of stromal cells, the induction of epithelial-to-mesenchymal transition in cancer cells, and the interaction with its cell surface receptor, CD44. Experimental studies using animal models have indicated that HA plays a crucial role in tumor growth and progression. Conditional transgenic mouse models, allowing HA synthase (HAS) over expression, display that HA overproduction influences rapid tumor growth through the recruitment of tumor-associated macrophages and fibroblasts. Consequently, the recruitment of both stromal cells plays an important cooperative role in tumor neovascularization. Supporting evidence has shown that the defect of HA synthesis in tumor associated fibroblasts impaired the recruitment of macrophages into tumor and subsequently attenuated angiogenesis and lymphangiogenesis. Thus, further investigations on the roles of HA in cancer pathogenesis may lead to new therapeutic strategies in cancer treatment.