Hyaluronan in Human Tumors: Importance of Stromal and Cancer Cell-Associated Hyaluronan

Publisher Summary Hyaluronan has turned out to be an active regulator of cell behavior rather than solely an inert extracellular matrix component. The high concentration of hyaluronan in many embryonic tissues correlates with their rates of cell migration and proliferation. Recent reports suggest that hyaluronan is not only a prognostic indicator, but also an active participant in the disease and a novel target of therapy. There is a large body of evidence from experimental animals and in vitro models suggesting that the production of hyaluronan by tumor cells is important for their malignant behavior. The assays on tumor biopsies do not give information about the dynamic processes that control the synthesis and catabolism of hyaluronan. Analyses of clinical patient materials show that alterations in the hyaluronan content, whether on the actual malignant cells or their surrounding stroma, are tightly associated with patient prognosis. Tumor progression is highly likely when hyaluronan is abundant on the surface or within tumor cells of gastric or colon carcinoma. There are number of ways hyaluronan can be involved in the regulation of cancer growth and spreading, as suggested by experiments on animals, and studies in vitro. However, understanding the relative importance of the various aspects of hyaluronan functions and metabolism in human cancers in vivo is still lacking and warrants more research on clinical materials.