Identification of novel drug resistance-associated proteins by a panel of rat monoclonal antibodies

MJ Flens, GL Scheffer, P vanderValk, HJ Broxterman, EWHM Eijdems, ACLM Huysmans, MA Izquierdo, RJ Scheper

    OnderzoeksoutputAcademicpeer review

    22 Citaten (Scopus)


    Since some multidrug-resistant (MDR) tumor cell lines show drug accumulation defects but do not over-express Pgp or MDR protein (MRP), a search was made for novel MDR-related transporter proteins by immunizing rats with nonsmall cell lung cancer SW-1573/2R120 cells to produce monoclonal antibodies (MAbs). Five rat MAbs (LMR-4, -12, -42, -44 and -94) were generated, showing strong membranous staining of non-Pgp MDR SW-1573/2R120 tumor cells and minimal reactivity to the corresponding parental and revertant cell lines. In addition, a 6th MAb (LMR-5) was isolated, recognizing the MDR-related lung resistance protein (LRP), previously identified as the major vault protein. The first 5 LMR MAbs show predominantly membranous staining of several non-Pgp MDR tumor cell lines of different histogenetic origins, except for LMR-4, which recognizes only MDR sublines of the SW-1573 cell line. Flow-cytometric analysis revealed that all MAbs, except LMR-4 and -5, detect outside epitopes. Functional studies showed that these MAbs did not restore the daunorubicin accumulation defect. All but one of the MAbs (LMR-42) showed staining of distinct normal human tissues, notably epithelial cells lining the airways and digestive tract. In addition, staining of vascular endothelial cells was found with all MAbs except LMR-4, Three MAbs (LMR-I2, -44 and -94) showed remarkable immunoreactivity with vincristine-selected SW-1573 sublines. By immunoblotting and precipitation, the LMR antigens were found to be in the 42-69 kDa range. (C) 1997 Wiley-Liss, Inc.

    Originele taal-2English
    Pagina's (van-tot)249-257
    Aantal pagina's9
    TijdschriftInternational Journal of Cancer
    Nummer van het tijdschrift2
    StatusPublished - 9-okt-1997

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