Immunohistochemical detection of P-glycoprotein in human tumor cells with a low degree of drug resistance

H. J. Broxterman, H. M. Pinedo, C. M. Kuiper, J. J M Van Der Hoeven, P. De Lange, J. J. Quak, R. J. Scheper, H. G. Keizer, G. J. Schuurhuis, J. Lankelma

Research output: Contribution to journalArticlepeer-review

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-I MAb. Subline SW 1573/50A 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 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.

Original languageEnglish (US)
Pages (from-to)340-343
Number of pages4
JournalInternational Journal of Cancer
Volume43
Issue number2
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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