Hyalurondiase: Both a tumor promoter and suppressor

Abstract

Originally termed as the "spreading factor", hyaluronidases (HAases) are present in a variety of toxins and venoms. For example, HAase is the virulent factor of beta-hemolytic Streptococci and it is also present in the venoms of snake, bee, wasp, scorpion, etc, where it aids in the spread of these venoms in the body. In mammals, testicular HAase present in the sperm acrosome is necessary for the fertilization of the ovum. 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 just about a year ago. In this part of the review, we will focus on the recent advances in our understanding of the role of HAases in cancer.

PPARα and PPARγ Coactivation Rapidly Induces Egr-1 in the Nuclei of the Dorsal and Ventral Urinary Bladder and Kidney Pelvis Urothelium of Rats

“…Heparanase and hyaluronidase play critical roles in the degradation of extracellular matrix and are frequently upregulated in malignant tumors Ogishima, Shiina, Breault, Tabatabai et al 2005;Ogishima, Shiina, Breault, Terashima et al 2005). Correspondingly, heparanase as well as hylaluronidase have been shown to promote bladder as well as prostate cancer development Lokeshwar and Selzer 2008;Ogishima, Shiina, Breault, Terashima et al 2005;Ogishima, Shiina, Breault, Tabatabai et al 2005). In fact, hyaluronidase activity is a recognized urinary biomarker for human bladder cancer (Vrooman and Witjes 2009).…”

“…Interestingly, while the available literature quoted above indicates that Egr-1 would promote rat bladder cancer, it is also known that Egr-1 may either inhibit or promote hyaluronidase expression depending on hyaluronidase promoter methylation . Also, strong overexpression of hyaluronidase may have anti-cancer effect (Lokeshwar and Selzer 2008). In short, there is strong albeit indirect evidence to support that early induction of Egr-1 in the urothelium of the bladder of rats may be relevant to later bladder cancer developent.…”

Snake Venom: A Potent Anticancer Agent

“…It is actually an endogycosidase as it degrades the beta-N-acetyl-glucosaminidic linkages in HA polymer (Lokeshwar and Selzer, 2008). It is virtually present in all snake venom and has been known as "spreading factor".…”

Hyaluronan Associated Inflammation and Microenvironment Remodelling Influences Breast Cancer Progression

“…HA is synthesized by three HAS isoforms, HAS1-3, which are located on different chromosomes but share from 57 to 80% sequence homology (Weigel et al, 1997, Lokeshwar and Selzer, 2008, Stern, 2008. The mature enzymes are multi-pass integral proteins, which are primarily located in the plasma membrane and catalyze polymerization of HA from the uridine diphosphate (UDP) sugars uridine diphosphate glucuronic acid (UDP-Glc-UA) and uridine diphosphate N-acetylglucosamine (UDP-GlcNAC).…”