Immunohistochemical detection of P-glycoprotein in human tumor cells with a low degree of drug resistance.
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.
Broxterman
H J
HJ
Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
Pinedo
H M
HM
Kuiper
C M
CM
van der Hoeven
J J
JJ
de Lange
P
P
Quak
J J
JJ
Scheper
R J
RJ
Keizer
H G
HG
Schuurhuis
G J
GJ
Lankelma
J
J
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D014750:Vincristine; D003630:Daunorubicin