Previous studies have shown that survivin, the smallest member of the IAP protein family, has a bifunctional role in cellular division and survival decisions. It is highly expressed at mitosis and is a critical factor for completion of mitotic cell division [
15,
16]. Survivin acts as a potent inhibitor of apoptotic and non-apoptotic cell death, and protects cells as a stress response factor against unfavourable environments. From a clinical point of view, the most interesting feature of survivin is the widely accepted concept of an "oncofetal" pattern of expression. While undetectable in most adult differentiated tissues, survivin is ubiquitously expressed during embryonal developement and highly re-expressed in cancer. In malignant tumors, survivin antagonizes programmed cell death, favours tumour-associated neovascularization, promotes cell proliferation and preserves cell viability [
11]. Disregarding the yet undefined molecular mechanisms, a large body of evidence has demonstrated that survivin has indeed a strong potential of antagonizing drug and radiation induced apoptosis [
25,
26]. In the current study, we report high expression of survivin in human chondrosarcoma. Furthermore,
in vitro experiments indicate a potential role in the tumor's pronounced resistance to chemotherapy. Our data shows homogeneous expression of survivin in all analysed human chondrosarcomas (Figure
1A-D), while in adult cartilage no or only low levels of survivin protein were detectable (Figure
1 F). Immunohistochemistry revealed a predominantly cytoplasmic pattern of staining in chondrosarcoma. Immunofluorescence of cultured chondrosarcoma cells confirmed the cytoplasmic subcellular localization of survivin protein (Figure
2), indicating survivin's involvement in extranuclear (i.e. proliferation independent) functions. Of note, recent publications on survivin emphasize the prognostic relevance of subcellular distribution of survivin gene expression. While the prognostic value of nuclear survivin expression in cancer remains unclear, high levels of cytoplasmic survivin protein seem to correlate with resistance to drug/radiation therapy and poor patient outcome [
27,
28]. The unfavourable prognosis related to cytoplasmic survivin might be associated with its reported extranuclear function (e.g. counteracting apoptosis), whereas nuclear survivin could rather promote cell proliferation [
29]. In this context it is of particular interest that effects of strongly active proapoptotic substances as doxorubicin are significantly reduced by survivin overexpression in SW1353 (Figure
7). Accordingly, downregulation of survivin resulted in increased rates of spontaneous and drug induced apoptosis (Figure
6). It is therefore tempting to speculate that survivin represents a key molecule in maintaining constitutive antiapoptotic activity in chondrosarcoma. In this context, it has been shown, that an upregulation of survivin protein did not increase cell proliferation or changed cell cycle distribution, while suppression of survivin resulted in a failure to exit mitosis, the previously described G
2/M-arrest [
21].