A UNIQUE HUMAN OVARIAN-CARCINOMA CELL-LINE EXPRESSING CD34 IN ASSOCIATION WITH SELECTION FOR MULTIDRUG-RESISTANCE

BACKGROUND. The role of P-glycoprotein (Pgp) in multidrug resistance ( MDR) is uncontested. Expression of Pgp on hematopoietic cells has been correlated with CD34 expression. For acute myeloid leukemia, the prog nostic value of Pgp for clinical response is at best equivalent to tha t of CD34. The current study investigated whether expression of CD34 c an be associated with selection for drug resistance. METHODS. Several established MDR cell lines were screened by flow cytometry for express ion of CD34. Human ovarian carcinoma cells (A2780), which simultaneous ly expressed CD34 and Pgp, were identified. Subsequent cloning resulte d in a new cell line (A2780-Dx5c) that expressed CD34 in the absence o f Pgp. Involvement of non-Pgp-mediated MDR mechanisms was assessed by immunohistochemistry (MRP and LRP), enzyme activity studies (glutathio ne pathway), cross-resistance patterns, and Northern blot (type II alp ha topoisomerase). RESULTS. A2780-Dx5c was cross-resistant to doxorubi cin, daunorubicin, idarubicin, and VP-16. However, unlike the Pgp-expr essing cells, it was not cross-resis rant to vincristine or amsacrine. The drug resistance was correlated with a decreased level of type II alpha topoisomerase in the A2780-Dx5c cell line compared with the pare ntal cell line. No evidence was found of involvement of MRP, LRP, or t he glutathione pathway with drug resistance in this cell line. CONCLUS IONS. A new cell line of nonhematopoietic and nonvascular endothelial origin that expresses CD34 in association with selection for MDR was c loned. A study of MDR mechanisms in this cell line revealed that reduc ed type II alpha topoisomerase levels were likely responsible for the MDR observed. A study of the causal relation between the selection of drug resistance and the expression of CD34 may provide insight into wh y CD34 correlates with poor clinical response in patients with acute m yeloid leukemia. (C) 1996 American Cancer Society.