Biological Effects of Calcium Hydroxyapatite Crystals in Breast Cancer
Final rept. 1 Aug 1997-31 Jul 2001
ROYAL COLL OF SURGEONS IN IRELAND DUBLIN
Pagination or Media Count:
For some time microcalcifications associated with breast lesions were considered to represent an epiphomenon, useful only as a radiological indicator of breast carcinoma. However, the data presented here shows that HA crystals are capable of exerting significant biological effects on surrounding cells. In this study we report that HA increases mitogenesis in both normal and malignant mammary cell lines. Particles of latex beads, of similar size and concentration to HA crystals, had no effect on mitogenesis. We have also shown that HA crystals stimulate mitogenesis of quiescent mammary cell lines in a concentration dependent fashion. HA crystals enhance the production of a variety of MMPs in normal and breast cancer cell lines alone or in co-culture. In addition our results suggest that exposure to HA crystals can cause a significant increase in PGE2 by induction of COX, which appears to be a critical factor in regulating the mitogenesis of those cells. Immunohistochemical staining of breast biopsies however did not show enhanced expression of MMP-1 or MMP-9 localised around the calcifications. COX-2 staining was occasionally upregulated in the proximity of a calcification and this finding warrants further study. Characterisation of the calcifications in the biopsies is necessary to help explain these finding. The data generated with the aid of this award supports our hypothesis that HA crystals may contribute to breast cancer progression by amplifying the pathological processes surrounding a lesion and underlie the importance of further studies of the pathological potential of microcalcifications consisting of HA crystals in breast oncology.
- Medicine and Medical Research