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

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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

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Broxterman, H. J., Pinedo, H. M., Kuiper, C. M., Van Der Hoeven, J. J. M., De Lange, P., Quak, J. J., Scheper, R. J., Keizer, H. G., Schuurhuis, G. J., & Lankelma, J. (1989). Immunohistochemical detection of P-glycoprotein in human tumor cells with a low degree of drug resistance. International Journal of Cancer, 43(2), 340-343.