Calcium HA can amplify the pathological process in breast cancer

Calcium HA can amplify the pathological process in breast cancer

(Breast Cancer-July 28, 2003)

Calcium HA can amplify the pathological process in breast cancer.

According to a study from Ireland, "Microcalcifications containing calcium hydroxyapatite (HA) are often associated with malignant human breast lesions. Frequently, they are the only mammographic features that indicate the presence of a tumoral lesion.

"We previously reported the induction of both mitogenesis and prostaglandin E-2 (PGE(2)) production and the increased activities of matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in normal human mammary epithelial cells and breast cancer cell lines, treated with HA," wrote M.M. Cooke and colleagues, Royal College of Surgeons, Ireland, Department of Clinical Pharmacology.

"In the present study we attempted to elucidate the mechanism of these biological effects. Firstly, we found that direct cell-crystal contact was required for induction of mitogenesis as the effect was not merely a result of isotopic exchange of calcium into the culture medium," the researchers wrote.

"Treatment with bafilomycin A(1), a proton pump inhibitor, abrogated HA-induced mitogenesis to control cell levels. These results suggest that phagocytosis and intracellular crystal dissolution is required for HA-induced mitogenesis," the researchers stated.

"We also demonstrated that the increase in prostaglandin E-2, previously reported, is due, at least in part, to HA-induced upregulation of cyclooxygenase-2 (COX-2) in Hs578T cells. An accumulation of MMP-1 mRNA was also shown in response to HA stimulation in Hs578T cells," they added.

"Furthermore, an HA-induced increase in interleukin-1beta (IL-1beta), a potent inducer of MMP-1 gene expression, was demonstrated in Hs578T cells at 2 and 4 h.," they stated.

The researchers concluded: "Treatment with phosphocitrate (PC) (a naturally occurring inhibitor of calcium phosphate crystallisation, which is known to block a number of HA-induced biological effects in other cell types) blocked HA-mediated mitogenesis, as well as, COX-2, MMP-1 and IL-1beta induction, at the transcriptional level. These results show that calcium HA crystals are capable of exerting significant biological effects on surrounding cells which can be abrogated by PC and emphasize the role of calcium HA in amplifying the pathological process involved in breast cancer."

Cooke and colleagues published the results of their research in Breast Cancer Research and Treatment (Phosphocitrate inhibits calcium hydroxyapatite induced mitogenesis and upregulation of matrix metalloproteinase-1, interleukin-1 beta and cyclooxygenase-2 mRNA in human breast cancer cell lines. Breast Cancer Res Treat, 2003;79(2):253-263).

For additional information, contact M.P. Morgan, Royal College of Surgeons Ireland, Department of Clinical Pharmacology, 123 St. Stephens Green, Dublin 2, Ireland.

The publisher of the journal Breast Cancer Research and Treatment can be contacted at: Kluwer Academic Publishing, Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands.

The information in this article comes under the major subject area of Oncology. This article was prepared by Health & Medicine Week editors from staff and other reports.