Expression of lung resistance protein in epithelioid sarcoma in vitro and in vivo

The incidence of epithelioid sarcoma among patients with malignant soft tis sue tumors is small, but the rates of recurrence and metastasis of this typ e of sarcoma are high, To date, effective chemotherapy for advanced epithel ioid sarcoma has not been established and, furthermore, epithelioid sarcoma is known to exhibit multidrug resistance (MDR). The chemosensitivities to anticancer agents of two cell lines established from epithelioid sarcoma we re examined in this study. The results showed that the ES-OMC-MN and SFT-86 06 cell lines were resistant to vincristine (IC50 1190 nM and 872 nM, respe ctively) and Adriamycin (IC50 921 nM and 650 nM, respectively), but sensiti ve to actinomycin D (IC50 < 10 nM). P-glycoprotein (p-Gp) and MDR-associate d protein (MRP) were not expressed in these cell lines, but a high expressi on level of lung resistance protein (LRP) was observed. The original tumor tissues from which the two cell lines were established were also found to b e LRP-positive but not to express p-Gp or MRP. Their chemosensitivities to Adriamycin were not significantly altered in the presence of 2.5 mu g/ml an ti-LRP antibody (LRP-56), but the IC50 of vincristine was much less (IC50 1 28 nM and 27 nM, respectively) than that for an untreated cell line, It is thus suggested that the vincristine resistance in the two cell lines is LRP -mediated, Since cyclosporin A. known to be a modifier of p-Gp, also induce d reversal of vincristine resistance in the ES-OMC-MN and SFT-8606 cell lin es (IC50 6.2 nM and 17 nM, respectively), it is suggested that cyclosporin A acts as a modifier of MDR mediated by LRP.