Abstract
Abstract Introduction: Aluminium [Al(III)] is the third most abundant element as well as the most abundant metal in the Earth's crust. The human population is exposed to Al throughout daily life; in drinking water, food, via application of antiperspirants, use of antacids and vaccination. However, aluminum exposure has been linked to a variety of pathological disorders like anemia, osteomalacia , hepatic disorder, and neurological disorder. In addition, studies report that aluminum levels are higher in tumors, including breast cancers than in surrounding normal tissues. This suggests that aluminum accumulation may provide some selective advantage to the tumor. Methods/Results:To determine how aluminum affects cells that reside in mammary tissue, we studied the in vitro effects of Al exposure on human mammary epithelial cells and mesenchymal cells. Cells used in our study included hTERT-immortalized human mammary epithelial cells (HMECs), the immortalized human mammary epithelial cell line (MCF10A), hTERT-immortalized reduction mammary fibroblasts (RMF/EG) and a dermal-derived human fibroblast cell line (MSU1.1). Using the MTT assay we found that AlCl3 and AlOH3 salts inhibit the growth of the mammary epithelial cells causing complete inhibition of proliferation at doses around 1mM and decreased proliferation was observed at doses as low as 12.8 uM. Surprisingly at these doses, Al salts caused dose-dependent increase in proliferation the mesenchymal cells. The proliferative effect of Al on mesenchymal cells was confirmed using clonogenic assay. Flow cytometric evaluation of cell cycle using PI/BrdU incorporation demonstrated that in MSU1.1 cells exposed to AlOH3 for 48 hrs, the percentage of cells in S phase of the cell cycle nearly doubled as compared to untreated cells (P <0.05). Similar results were seen with AlCl3 treatment of MSU1.1 and AlOH3/AlCl3 treatment of RMF/EG cells. Conclusions: These data indicate that while Al salts induce dose dependent cytotoxicity in human epithelial cell lines, they induce proliferation of mesenchymal cells. The tumor microenvironment, including a proliferative stroma, is known to facilitate mammary carcinogenesis. Our data suggest that Al accumulation could promote the development of a permissive microenvironment. We are currently seeking to determine the mechanism for the differential effect of Al in cells and whether this effect influences transformation or carcinogenesis. Citation Format: Manar A. AbdelMageed, Parthena Foltopoulou, Monica Betancur-Boissel, Elizabeth A. McNiel. Differential effects of aluminum exposure on epithelial and mesenchymal cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1157. doi:10.1158/1538-7445.AM2014-1157
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