This concept predicts that disruption of HA-CD44 signaling would inhibit disease progression in patients whose tumors overexpress HAS2. In the studies reported here we assessed whether 1,25D3 regulates HAS2 in cellular models of human breast cancer, and whether suppression of HAS2 by 1,25D3 is sufficient to inhibit HA synthesis in the context of aggressive disease. Here, HAS2 is linked to breast carcinoma.