title: Immunohistochemical detection of P-glycoprotein in human tumor cells with a low degree of drug resistance.
abstract: We report the immunohistochemical detection of the 170-180 kDa multi-drug-resistance-related P-glycoprotein in human tumor cells with a low level of resistance. A series of human squamous lung cancer cell lines with increasing levels of resistance to doxorubicin (DOX) was developed and stained for P-glycoprotein, using the JSB-IMAb. Subline SW1573/50A with a 4- to 6-fold cross-resistance to daunorubicin (DNR) and vincristine (VCR) showed rather uniform positive staining for P-glycoprotein apparently at cytoplasmic sites. Only in cells with higher degrees of resistance (greater than 10-fold) could plasma-membrane-associated P-glycoprotein be made visible. DNR efflux was increased in SW1573/50A as compared to the parent line SW1573 (52 and 70% DNR were retained during 3 min efflux respectively). Verapamil partially reversed DNR and VCR resistance in SW1573/50A. Cells obtained from a metastasized renal cell carcinoma and cultured in vitro stained in a similar way to SW1573/50A and showed some sensitivity to verapamil modulation of VCR cytotoxicity. Our results suggest that weakly resistant cancer cells obtained from patients can be routinely detected with JSB-I on cytospins, and implicate that in such weakly resistant cells P-glycoprotein may be present, while plasma membrane expression is not yet readily detectable.
authors.affiliation: Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Broxterman
authors.forename: H M
authors.initials: HM
authors.lastname: Pinedo
authors.forename: C M
authors.initials: CM
authors.lastname: Kuiper
authors.forename: J J
authors.initials: JJ
authors.lastname: van der Hoeven
authors.forename: P
authors.initials: P
authors.lastname: de Lange
authors.forename: J J
authors.initials: JJ
authors.lastname: Quak
authors.forename: R J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: H G
authors.initials: HG
authors.lastname: Keizer
authors.forename: G J
authors.initials: GJ
authors.lastname: Schuurhuis
authors.forename: J
authors.initials: J
authors.lastname: Lankelma
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D000911:Antibodies, Monoclonal; D002292:Carcinoma, Renal Cell / Q000032:analysis / Q000378:metabolism*; D003630:Daunorubicin / Q000378:metabolism*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000032:analysis / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000276:immunology; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D014750:Vincristine; D003630:Daunorubicin