Calcium hydroxyapatite promotes mitogenesis and matrix metalloproteinase expression in human breast cancer cell lines

Radiographic mammary microcalcifications are one of the most pertinent diag nostic markers of breast cancer. Breast tissue calcification in the form of calcium hydroxyapatite (HA) is strongly associated with malignant disease. We tested the hypothesis that calcium HA may exert biological effects on s urrounding cells, thereby facilitating breast cancer progression. Our findi ngs showed that HA crystals enhanced mitogenesis in breast cancer cell line s MCF-7 and Hs578T and also in normal human mammary epithelial cells. HA cr ystals were also found to upregulate the production of a variety of matrix metalloproteinases (MMPs), including MMP-2, -9, and -13 in MCF-7 and MMP-9 In human mammary epithelial cell lines. HA crystals were found to greatly a ugment prostaglandin E-2 levels in Hs578T cells, and treatment with a cyclo oxygenase inhibitor, aspirin, abrogated the HA-induced mitogenesis. These r esults suggest that calcium HA crystals may play an active role in amplifyi ng the pathological process involved in breast cancer. (C) 2001 Wiley-Liss, Inc.