Abstract
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.
Original language | English |
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Pages (from-to) | 249-257 |
Number of pages | 9 |
Journal | International Journal of Cancer |
Volume | 73 |
Issue number | 2 |
Publication status | Published - 9-Oct-1997 |
Keywords
- CANCER CELL-LINES
- HUMAN TUMOR-CELLS
- P-GLYCOPROTEIN
- MULTIDRUG-RESISTANCE
- EXPRESSION
- OVEREXPRESSION
- TRANSPORTER
- MRP
- ACCUMULATION
- MEMBRANE