Abstract
BackgroundChemotherapy-induced cell death can involve the induction of apoptosis. Thus, aberrant function of the pathways involved might result in chemoresistance. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis) in human osteosarcoma would result in resistance to chemotherapy.MethodsOsteosarcoma cell lines (SAOS-2 and TE-85) obtained from ATCC and were maintained in complete Eagle's MEM medium. Suspension culture was established by placing cells in tissue culture wells coated with poly-HEMA. Cell cytotoxicity was determined using a live/dead cytotoxicity assay. Cell cycle/apoptosis analyses were performed using propidium iodide (PI) staining with subsequent FACS analysis. Apoptosis was also assayed by Annexin-FITC/PI staining.ResultsEtoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended). Moreover, suspended anoikis resistant TE-85 cells (TE-85ar) retained their sensitivity to chemotherapy as well.ConclusionAcquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators.
Highlights
Chemotherapy-induced cell death can involve the induction of apoptosis
Since the general acquisition of apoptosis resistance would affect both de-adhesion and chemotherapy-induced cell death, we investigated whether acquisition of anoikis resistance conferred general resistance to other apoptotic inducers or was independent of these other apoptotic pathways
We have previously shown that SAOSp and SAOSar cells attached to the extracellular matrix (ECM) are sensitive to induction of apoptosis and die after treatment with staurosporine, cycloheximide and hydrogen peroxide[18]
Summary
Chemotherapy-induced cell death can involve the induction of apoptosis. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis) in human osteosarcoma would result in resistance to chemotherapy. During normal organ development apoptosis provides an efficient mechanism whereby unwanted cells are "discretely" eliminated. The functions that ensure proper activation of apoptosis are somehow lost during tumorigenesis, allowing cancer cells to proliferate indefinitely and in an uncontrolled fashion[1,2]. The term anoikis defines the type of apoptosis induced after proper adherence to the extracellular matrix (ECM) is denied[3,4]. Attachment to the ECM is mainly mediated by integrins; a family of heterodimeric transmembrane receptors composed of an alpha and a beta chain. In response to physiological clues, bidirectional integrin signaling mediates cell (page number not for citation purposes)
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