LS14 cells: a model for chemoresistance in liposarcoma.
Liposarcoma, a malignancy of adipose tissue, is the most common soft tissue sarcoma. Patients whose primary tumor cannot be resected or those who have developed metastasis, have poor prognosis since liposarcomas are highly resistant to chemotherapy. We recently generated a spontaneously immortalized cell line, named LS14, from a patient with metastatic liposarcoma. Our goal was to compare the responsiveness of LS14 and SW872 liposarcoma cells to anti-cancer drugs and explore mechanisms of chemoresistance. Using complementary assays for cell viability and number we found that SW872 cells responded robustly to relatively low concentrations of doxorubicin, cisplatin and vinblastine. This reduction in cell viability was due to apoptosis, as evident by phosphatidylserine exposure and caspase 3 cleavage. In contrast, only a high dose of doxorubicin or combination therapy effectively reduced LS14 cell viability and induced apoptosis. LS14 cells showed a higher expression of Bcl-2 and Bcl-xL, but a lower expression of survivin and Bax, than SW872 cells, suggesting that anti-apoptotic proteins contribute to chemoresistance in LS14 cells. Although LS14 cells did not form colonies in soft agar, they generated large tumors and metastases in SCID mice, establishing their tumorigenicity in vivo. In conclusion, LS14 cells are much more resistant to chemotherapy than SW872 cells, making them an excellent model for exploring the efficacy and mechanism of action of anti-cancer drugs in liposarcomas.
LaPensee
Elizabeth W
EW
Department of Cell and Cancer Biology, University of Cincinnati, Ohio 45267-0521, USA.
Reddy
Shamantha P
SP
Hugo
Eric R
ER
Schwemberger
Sandy J
SJ
Ben-Jonathan
Nira
N
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008080:Liposarcoma; D051379:Mice; D016513:Mice, SCID; D008954:Models, Biological; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins