Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents.
BACKGROUND
Chemotherapy-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.


METHODS
Osteosarcoma 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.


RESULTS
Etoposide, 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.


CONCLUSIONS
Acquisition 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.
Díaz-Montero
C Marcela
CM
Department of Immunology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. mdiamon@mdanderson.org
McIntyre
Bradley W
BW
D023102:Anoikis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D002469:Cell Separation; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D000860:Hypoxia; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology; D011419:Propidium / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
D000970:Antineoplastic Agents; D011419:Propidium; D014747:Vinblastine; D005047:Etoposide; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin