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Immunohistochemical detection of P‐glycoprotein in human tumor cells with a low degree of drug resistance
Author(s) -
Broxterman Henricus J.,
Pinedo Herbert M.,
Kuiper Catharina M.,
Van Der Hoeven Jacobus J. M.,
De Lange Pieter,
Quak Jasper J.,
Scheper Rik J.,
Keizer Hiskias G.,
Schuurhus Gerrit Jan,
Lankelma Jan
Publication year - 1989
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910430229
Subject(s) - p glycoprotein , daunorubicin , efflux , immunohistochemistry , verapamil , cell culture , in vitro , glycoprotein , vincristine , doxorubicin , drug resistance , cytotoxicity , biology , microbiology and biotechnology , multiple drug resistance , cancer research , immunology , medicine , chemotherapy , leukemia , biochemistry , genetics , calcium , cyclophosphamide
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‐lMAb. 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 (> 10‐fold) could plasmamembrane‐associated P‐glycoprotein be made visible. DNR efflux was increased in SW1573I50A as compared to the parent line SWl573 (52 and 70% DNR were retained during 3 min efflux respectively). Verapamil partially reversed DNR and VCR resistance in SWl573/50A. Cells obtained from a metastasized renal cell carcinoma and cultured in vitro stained in a similar way to SWl573/50A 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‐l on cytospins, and Implicate that in such weakly resistant cells P‐glycoprotein may be present, while plasma membrane expression is not yet readily detectable.