Increased expression of beta 2-microglobulin in multidrug-resistant tumour cells.
The rat monoclonal antibody LMR-12 was shown earlier to react with a plasma membrane protein, upregulated in multidrug-resistant cell lines. In this study, we observed distinct LMR-12 staining in 36 out of 55 non-drug-selected tumour cell lines, including melanomas, renal cell-, colon- and lung carcinomas, whereas in other tumour types, such as leukaemia and ovarian cancer, LMR-12 staining was generally low or absent. The cDNA encoding the LMR-12 antigen was isolated from a library of the multidrug-resistant human fibrosarcoma cell line HT1080/DR4 by expression cloning in MOP8 cells. Sequence analysis showed that the LMR-12 antigen is identical to the major histocompatibility complex class I molecule beta 2-microglobulin (beta2-m). The LMR-12/ beta2-m staining results were confirmed by mRNA microarray data from an independent National Cancer Institute study, as well as by newly obtained reverse transcriptase polymerase chain reaction data. Further analysis of the microarray data showed that beta2-m levels closely reflected levels of major histocompatibility complex class I heavy chains and the transporter associated with antigen processing. Since the ABC transporter associated with antigen processing was previously shown to contribute to multidrug-resistance, it may very well be that the observed LMR-12/ beta2-m levels are secondary to (elevated) levels of the transporter associated with antigen processing. A perspective arising from the present study is that drug resistant tumour cells may, by having elevated levels of major histocompatibility complex related molecules, be particular good candidates for alternative therapeutic therapies, such as cytotoxic T cell mediated immune-therapies.
Scheffer
G L
GL
Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands. rj.scheper@vumc.nl
de Jong
M C
MC
Monks
A
A
Flens
M J
MJ
Hose
C D
CD
Izquierdo
M A
MA
Shoemaker
R H
RH
Scheper
R J
RJ
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017931:DNA Primers / Q000737:chemistry; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005434:Flow Cytometry; D015723:Gene Library; D006801:Humans; D007124:Immunoenzyme Techniques; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D001613:beta 2-Microglobulin / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D001613:beta 2-Microglobulin