%0 Journal Article
%T Sensitization of interferon-¦Ã induced apoptosis in human osteosarcoma cells by extracellular S100A4
%A Kjetil Pedersen
%A Kristin Andersen
%A £¿ystein Fodstad
%A Gunhild M£¿landsmo
%J BMC Cancer
%D 2004
%I BioMed Central
%R 10.1186/1471-2407-4-52
%X Cell cultures from two human osteosarcoma cell lines, OHS and its anti-S100A4 ribozyme transfected counterpart II-11b, was treated with IFN-¦Ã and recombinant S100A4 in order to study the sensitizing effects of extracellular S100A4 on IFN-¦Ã mediated apoptosis. Induction of apoptosis was demonstrated by DNA fragmentation, cleavage of poly (ADP-ribose) polymerase and Lamin B.In the present work, we found that the S100A4-expressing human osteosarcoma cell line OHS was more sensitive to IFN-¦Ã-mediated apoptosis than the II-11b cells. S100A4 protein was detected in conditioned medium from OHS cells, but not from II-11b cells, and addition of recombinant S100A4 to the cell medium sensitized II-11b cells to apoptosis induced by IFN-¦Ã. The S100A4/IFN-¦Ã-mediated induction of apoptosis was shown to be independent of caspase activation, but dependent on the formation of reactive oxygen species. Furthermore, addition of extracellular S100A4 was demonstrated to activate nuclear factor-¦ÊB (NF-¦ÊB).In conclusion, we have shown that S100A4 sensitizes osteosarcoma cells to IFN-¦Ã-mediated induction of apoptosis. Additionally, extracellular S100A4 activates NF-¦ÊB, but whether these events are causally related remains unknown.The S100 protein family consists of at least 21 small, acidic, Ca2+-binding proteins with different expression patterns and apparently diverse functional and biological properties [1]. The S100A4 protein has been associated with increased metastatic capacity of cancer cells [2-4], but how S100A4 exerts the metastasis-promoting effects is still incompletely understood. S100A4 has been shown to interact with a number of cytoskeleton-associated proteins, including non-muscle myosin [5], actin [6] and non-muscle tropomyosin [7], thereby possibly affecting cell motility. In addition, we have previously demonstrated an association between S100A4, matrix metalloproteinases and the invasive capacity of osteosarcoma cells [8]. It has also been reported that S100A4 can be sec
%U http://www.biomedcentral.com/1471-2407/4/52