Increased expression of beta 2-microglobulin in multidrug-resistant tumour cells

Abstract

The rat monoclonal antibody LMR-12 was shown earlier to react with a plasma membrane protein, upregulated in multidrugresistant 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 (b 2 -m). The LMR-12/ b 2 -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 b 2 -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/ b 2 -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.

Upregulation of ASCL1 and inhibition of Notch signaling pathway characterize progressive astrocytoma

“…In accordance with previous findings, we found Osteonectin and Vimentin to be upregulated in the majority of all grades of astrocytoma (Sallinen et al, 2000;Ljubimova et al, 2001;Fathallah-Shaykh et al, 2002). Although differential regulation of b2-microglobulin has been reported in diffuse large-B-cell lymphoma (Jordanova et al, 2003) and multidrug resistance phenotype in tumor cells (Scheffer et al, 2002), we found b2-microglobulin to be upregulated in GBM. Another gene, Semaphorin 4D, which has a functional role in the immune system (Hall et al, 1996) as well as in the nervous system (Kumanogoh et al, 2002), is found to be downregulated in astroctyomas.…”

Identification of β2‐microglobulin as a urinary biomarker for chronic allograft nephropathy using proteomic methods

“…β2 Microglobulin has been identified previously as a marker of other diseases e.g. tubulointerstitial disease 40, acute renal transplant rejection 33, drug toxicity 41, autoimmune diseases 42, 43, and lymphoproliferative diseases 44, 45. As β2 microglobulin is a good urinary biomarker to assess proximal tubular function, this may explain the reason why along with the accompanying biomarker tree it is a significant biomarker in this study due to the tubulointerstitial injury present in CAN.…”

Identification of beta2-microglobulin as a potential target for ovarian cancer

“…25 In addition, b2M also functions in creating multidrug-resistance. 26 Recent studies demonstrated that b2M has direct mitogenic activities as a growth promoting soluble factor for human renal cancer cells in vitro via PKA/CREB activation, VEGF signaling, and cell survival signaling, including the PI3K/Akt and MAPK pathways. 27 The expression levels of b2M were positively correlated with cancer cell growth, survival and migration in b2M overexpressing transfectants.…”