Hyaluronidase: Both a Tumor Promoter and Suppressor

Hyaluronidases (HAases) are a class of enzymes that predominantly degrade hyaluronic acid (HA) and are present in a variety of toxins and venoms. Despite a lot of work on bacterial, invertebrate, and testicular HAases, a connection between HAase and cancer was unequivocally established just over a decade ago and the functional significance of HAases in cancer was demonstrated. This chapter concerns the recent advances in the understanding of the role of HAases in cancer. Various studies have established a link between HAase and the tumor invasive/metastatic phenotype. HAase expression appears to be elevated in many carcinomas and the expression correlates with tumor invasiveness. However, in some carcinomas HAase expression depends on the status of the chromosome 3p21.3 locus and may inversely correlate with tumor grade. The origin of the concept that HAeses are tumor suppressors lies in the observation that in some epithelial carcinomas, the 3p21.3 locus is deleted. The diagnostic potential of HAase, either alone or together with HA, has been extensively explored in bladder cancer. Standard clinical and pathological parameters provide very limited information to clinicians regarding which prostate cancers will progress and/or have a poor prognosis.