Association of hyaluronidase and breast adenocarcinoma invasiveness

Hyaluronic acid (HA) is a component of the extracellular matrix (ECM) that exists as a high molecular weight polymer composed of alternating disacchar ides, D-glucuronic acid and N-acetyl D-glucosamine. The interaction of hyal uronidase with HA results in the disruption of basement membrane integrity and produces an angiogenic response that has been implicated in tumor invas iveness and metastasis. Although hyaluronidase is present in several neopla sms, levels of hyaluronidase expression in breast cancer are not known. Thi s investigation defines the correlation of elevated levels of hyaluronidase with breast adenocarcinoma invasiveness. Utilizing RT-PCR, RNA was extract ed from paraffin embedded tissues (n=6) of patients diagnosed with fibrocys tic breast changes, ductal carcinoma in situ (DCIS), and invasive adenocarc inoma. After constructing cDNA primers for base pairs 504 and 759 of the PH -20 gene (which is homologous to the hyaluronidase gene), PCR was performed and the products were visualized with ethidium bromide using gel electroph oresis. Invasive breast adenocarcinoma had a significantly higher level of hyaluronidase expression compared to other breast tissue samples; (32+/-15 vs. 8+/-3; p<0.03). Elevated levels of hyaluronidase correlated with invasi ve breast adenocarcinoma. Our data suggests that elevated levels of hyaluro nidase are associated with breast adenocarcinoma invasive potential. Hyalur onidase may play an integral role in breast cancer invasion and metastasis.