Glucosylceramide: A marker for multiple-drug resistant cancers

Background: Multiple-drug resistance (MDR) is a major reason for chemotherapy failure. Herein we describe glucosylceramide, a new marker for MDR. Methods: Cellular lipids were analyzed in three human MDR cancel cell lines and their drug-sensitive counterparts. Analysis of glucosylceramide was also performed in six melanoma specimens and one breast tumor specimen obtained from patients who had undergone chemotherapy. Glucosylceramide, analyzed by mass and by cellular utilization of radiolabeled precursor ([³Hpalmitic acid), was isolated by lipid extraction techniques and resolved from other components by thin-layer chromatography. Results: Glucosylceramide was present consistently in all MDR cell lines and was absent, or present only at very low levels, in the corresponding drug-sensitive cells. Examination of human tumor specimens documented presence of the marker in all patients who had failed chemotherapy, and absence of the marker in each of the patients with known clinical response to chemotherapy. The response to chemotherapy was followed for a median of 8 months in melanoma patients and for 22 months in the breast cancer patient. Conclusion: These findings suggest that glucosylceramide may hold clinical significance for the early identification of drug-resistant tumors.