Abstract
BackgroundThe prognosis of patients with Ewing sarcoma (ES) has improved over the course of the last decades. However, those patients suffering from metastatic and recurrent ES still have only poor chances of survival and require new therapeutic approaches. Interleukin-6 (IL6) is a pleiotropic cytokine expressed by immune cells and a great variety of cancer cells. It induces inflammatory responses, enhances proliferation and inhibits apoptosis in cancer cells, thereby promoting chemoresistance.MethodsWe investigated expression of IL6, its receptors and the IL6 signal transduction pathway in ES tumor samples and cell lines applying reverse transcriptase PCR, immunoblot and immunohistochemistry. The impact of IL6 on cell viability and apoptosis in ES cell lines was analyzed by MTT and propidium iodide staining, migration assessed by chorioallantoic membrane (CAM) assay.ResultsImmunohistochemistry proved IL6 expression in the stroma of ES tumor samples. IL6 receptor subunits IL6R and IL6ST were expressed on the surface of ES cells. Treatment of ES cells with rhIL6 resulted in phosphorylation of STAT3. rhIL6 protected ES cells from serum starvation-induced apoptosis and promoted migration. IL6 blood serum levels were elevated in a subgroup of ES patients with poor prognosis.ConclusionsThese data suggest that IL6 contributes to ES tumor progression by increasing resistance to apoptosis in conditions of cellular stress, such as serum starvation, and by promotion of metastasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1564-7) contains supplementary material, which is available to authorized users.
Highlights
The prognosis of patients with Ewing sarcoma (ES) has improved over the course of the last decades
Analysis of gene expression data from ES cell lines after inhibition of EWS-FLI1 expression demonstrated that several mediators of inflammation, including SOCS3, IL6ST, IL-1-accessory protein and IL-8 are regulated by EWS-FLI1 [5]
Diagnosis of Ewing sarcoma was made based on histological appearance, cytogenetics and RT-PCR for EWS-ETS fusion; all tumors were reviewed by a reference pathologist within the EURO-Ewing study
Summary
The prognosis of patients with Ewing sarcoma (ES) has improved over the course of the last decades. Those patients suffering from metastatic and recurrent ES still have only poor chances of survival and require new therapeutic approaches. Interleukin-6 (IL6) is a pleiotropic cytokine expressed by immune cells and a great variety of cancer cells. It induces inflammatory responses, enhances proliferation and inhibits apoptosis in cancer cells, thereby promoting chemoresistance. Over the course of the last 20 years survival rates for patients with Ewing sarcoma have increased as a consequence of therapy intensification, improvement of surgical techniques and radiotherapy. Elevated IL6 levels in peripheral blood of patients with bone sarcomas correlate with higher tumor extension and decreased overall survival [10]
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