Small fragments of HA, generated by Hyaluronidase, stimulate angiogenesis. In tumor tissues, it may promote tumor growth and metastasis probably by actively supporting tumor cell migration and offering protection against immune surveillance. HAases are a class of enzymes that predominantly degrade HA, they are endoglycosidases, as they degrade the b-N-acetyl-Dglucosaminidic linkages in the HA polymer. HAase has been shown to alter the expression of CD44 isoforms, which may also be involved in tumor progression. In addition, HAase is associated with increased tumor cell cycling. The HAase levels serve as an accurate marker for detecting prostate and bladder tumors. In humans, six HAase genes have been identified. Hyaluronidase-1 was originally purified from human plasma and urine, it is the major tumor-derived HAase expressed in bladder and prostate cancer tissues, and it has characterized expression at the mRNA and protein levels in tumor cells. HYAL1 is a,55–60 kDa protein, and it is consisted with 435 amino acids. An elevated level of HYAL1 has been found in prostate, bladder, breast, head and neck cancers, etc. HYAL1 was the first HAase to be recognized as being expressed by tumor cells and its expression correlates with their invasive and metastatic potential. No HYAL1 expression is observed in the tumor-associated stroma, although HYAL1 expression BEZ235 appears to correlate and perhaps induce HA production in the tumor-associated stroma. Among the six HAases, HYAL1 and Hyaluronidase-2 are widely distributed to degrade high molecular weight HA. The HYAL2 cleaves high MW HA into,20 kDa HA fragments, which are transported intracellularly and further digested into low MW HA fragments by HYAL1. The small angiogenic HA fragments stimulate endothelial cell proliferation, adhesion and migration by activating the focal adhesion kinase and mitogen-activated protein kinase pathways. HYAL1 has been found as an independent predictor of biochemical recurrence. HAase levels also increase in breast cancer cells when they become metastatic. We previously demonstrated that HYAL1 protein and activity were overexpression in breast cancer tissues and cells, and breast cancer cells with higher HAase expression, exhibited significantly higher invasion ability through matrigel than those cells with lower HAase expression. Knockdown of HYAL1 expression in breast cancer cells resulted in decreased cell growth, adhesion, invasion and angiogenesis.