Subcellular distribution of S100 proteins in tumor cells and their relocation in response to calcium activation

S100 proteins, a subgroup of the EF-hand Ca2+-binding protein family, regul ate a variety of cellular processes via interaction with different target p roteins. Several pathological disorders, including cancer, are linked to al tered Ca2+ homeostasis and might involve the multifunctional S100 proteins, which are expressed in a cell- and tissue-specific manner. The present wor k demonstrates a distinct intracellular localization of S100A6, S100A4, and S100A2 in two tumor cell lines derived from metastatic epithelial breast a denocarcinoma (MDA-MB231) and cervical carcinoma (HeLa). Treatment of the c ells by thapsigargin, the ionophore A23187, or cyclic ADP-ribose, to increa se [Ca2+](i) via different pathways, led to relocation of S100A6 and S100A4 but only partially of the nuclear S100A2, as demonstrated by confocal lase r scanning microscopy. These findings support the hypothesis that S100 prot eins could play a crucial role in the regulation of Ca2+ homeostasis in can cer cells.