Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

Breast cancer microcalcification-induced local inflammation; potential consequences for tumour progression

Maria Morgan, Molecular & Cellular Therapeutics. Keywords: cancer, breast cancer, cell biology, immunology.

Radiographic mammary microcalcifications constitute one of the most important diagnostic markers of both benign and malignant lesions of the breast. Up to 50% of all nonpalpable breast cancers are detected solely through microcalcifications presenting during a mammogram scan and up to 93% of cases of ductal carcinoma in situ (DCIS) present with microcalcifications. During the past decade, cases of subclinical cancer, that is, nonpalpable breast cancers detected by mammography, have accounted for a progressively increasing percentage of breast cancers. Although the diagnostic value of these microcalcifications in breast cancer is well established, their genesis is not clear. With the exception of our recent publications, there have been no other reported investigations of the mechanism of calcium deposition or, the potential of differing mammary cell types to generate specific calcium mineral species. No study to date has examined the pro-inflammatory potential of the deposited hydroxyapatite found associated with breast cancer. Furthermore, the potential for mineralisation and the microenvironment regulating it representing a significant feature of selected tumours has not even been considered. Many recent publications link initiation and recurrence of cancer to chronic inflammation[4, 5]. Macrophages are well known for their role in the primary response to infection and injury, but recently they have been implicated in the pathogenesis of tumour progression. We hypothesise that microcalcifications in the form of hydroxyapatite deposits are potent pro-inflammatory molecules and that in this context they promote M1 differentiation and may contribute to tumor progression. Thus this project will address (a) the role of hydroxyapatite in M1/M2 macrophage differentiation and (b) the potential biological consequences of hydroxyapatite-derived macrophages (and the cytokines they produce) in exacerbating tumor progression.

Mentors Maria Morgan. mmorgan@rcsi.ie