A unique human ovarian carcinoma cell line expressing CD34 in association with selection for multidrug resistance

Hans Minderman; Udo Vanhoefer; Karoly Toth; M. Denice Minderman; Youcef M. Rustum

doi:10.1002/(SICI)1097-0142(19961201)78:11<2427::AID-CNCR22>3.0.CO;2-1

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A unique human ovarian carcinoma cell line expressing CD34 in association with selection for multidrug resistance

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A unique human ovarian carcinoma cell line expressing CD34 in association with selection for multidrug resistance

Hans Minderman, Udo Vanhoefer, Karoly Toth, M. Denice Minderman and Youcef M. Rustum

Cancer, Vol.78(11), pp.2427-2436

12/01/1996

DOI: 10.1002/(SICI)1097-0142(19961201)78:11<2427::AID-CNCR22>3.0.CO;2-1

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Abstract

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 prognostic value of Pgp for clinical response is at best equivalent to that of CD34. The current study investigated whether expression of CD34 can be associated with selection for drug resistance. METHODS Several established MDR cell lines were screened by flow cytometry for expression of CD34. Human ovarian carcinoma cells (A2780), which simultaneously expressed CD34 and Pgp, were identified. Subsequent cloning resulted in a new cell line (A2780‐Dx5c) that expressed CD34 in the absence of Pgp. Involvement of non‐Pgp‐mediated MDR mechanisms was assessed by immunohistochemistry (MRP and LRP), enzyme activity studies (glutathione pathway), cross‐resistance patterns, and Northern blot (type IIα topoisomerase). RESULTS A2780‐Dx5c was cross‐resistant to doxorubicin, daunorubicin, idarubicin, and VP‐16. However, unlike the Pgp‐expressing cells, it was not cross‐resistant to vincristine or amsacrine. The drug resistance was correlated with a decreased level of type IIα topoisomerase in the A2780‐Dx5c cell line compared with the parental cell line. No evidence was found of involvement of MRP, LRP, or the glutathione pathway with drug resistance in this cell line. CONCLUSIONS A new cell line of nonhematopoietic and nonvascular endothelial origin that expresses CD34 in association with selection for MDR was cloned. A study of MDR mechanisms in this cell line revealed that reduced type IIα 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 why CD34 correlates with poor clinical response in patients with acute myeloid leukemia. Cancer 1996;78:2427‐36.

CD34

LRP

MRP

multidrug resistance

P‐glycoprotein

topoisomerase‐II‐α

Details

Title: Subtitle: A unique human ovarian carcinoma cell line expressing CD34 in association with selection for multidrug resistance
Creators: Hans Minderman - Roswell Park Cancer Institute
Udo Vanhoefer - Department of Internal Medicine, West German Cancer Center, University of Essen, Essen, Germany.
Karoly Toth - Roswell Park Cancer Institute
M. Denice Minderman - Roswell Park Cancer Institute
Youcef M. Rustum - Roswell Park Cancer Institute
Resource Type: Journal article
Publication Details: Cancer, Vol.78(11), pp.2427-2436
DOI: 10.1002/(SICI)1097-0142(19961201)78:11<2427::AID-CNCR22>3.0.CO;2-1
ISSN: 0008-543X
eISSN: 1097-0142
Publisher: Wiley Subscription Services, Inc., A Wiley Company
Number of pages: 10
Grant note: NIH (CA13038) American Cancer Society (DHP‐115) Cancer Center Core (CA16056) West German Cancer Foundation
Language: English
Date published: 12/01/1996
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984359959902771

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