Elevated soluble MUC1 levels and decreased anti-MUC1 antibody levels in patients with multiple myeloma

Abstract

Soluble MUC1 (sMUC1) levels are elevated in many MUC1+cancers. We and others have shown that MUC1 is expressed on multiple myeloma (MM) plasma cells and B cells. In this study, we measured sMUC1 levels in bone marrow (BM) plasma from 71 MM patients and 21 healthy donors (HDs), and in peripheral blood (PB) plasma from 42 MM patients and 13 HDs using an immunoassay that detects the CA27.29 epitope of MUC1. sMUC1 levels were found to be significantly greater (mean 31.76 U/mL, range 5.69 to 142.48 U/mL) in MM patient BM plasma versus HD BM plasma (mean 9.68 U/mL, range 0.65 to 39.83 U/mL) (P < .001). Importantly, BM plasma sMUC1 levels were related to tumor burden because sMUC1 levels were significantly higher for MM patients with active disease (34.62 U/mL, range 5.69 to 142.48 U/mL) versus MM patients with minimal residual disease (16.16 U/mL, range 5.7 to 56.68 U/mL) (P = .0026). sMUC1 levels were also elevated in the PB plasma of MM patients (32.79 U/mL, range 4.15 to 148.84 U/mL) versus HDs (18.47 U/mL, range 8.84 to 42.49) (P = .0052). Lastly, circulating immunglobulin M (IgM) and IgG antibodies to MUC1 were measured in 114 MM patients and 31 HDs, because natural antibodies to MUC1 have been detected in patients with other MUC1-bearing malignancies. These studies demonstrated lower levels of circulating IgM (P < .001) and IgG (P = .078) antibodies to MUC1 in MM patients compared with HDs. Our data therefore show that in MM patients, sMUC1 levels are elevated and correlate with disease burden, whereas anti-MUC1 antibody levels are decreased.

Form and pattern of MUC1 expression on T cells activated in vivo or in vitro suggests a function in T‐cell migration

“…The HMFG1 antibody, which can recognize MUC1 carrying extended core 2-based O-glycans, as well as cancer-associated glycoforms, also did not bind to resting T cells. Our findings are substantiated by other studies that demonstrated minimal staining of Jurkat cells using DF3-P and no staining of resting T cells with MUC1-specific mAbs VU-4H5 and VU-3C6, 20 and no staining of resting T cells with MUC1-specific mAb B27Á29. 18 Therefore, the majority of published reports support our observation that MUC1 is not expressed by resting human T cells.…”

“…Although the expression of MUC1 was originally thought to be restricted to epithelial tissues, recent work has suggested that MUC1 is also expressed by T and B cells. [18][19][20] The expression of MUC1 on such cells has implications for both immune tolerance and autoimmunity. We therefore sought to investigate in detail the expression of MUC1 in human T cells, documenting both the level and duration of expression, the distribution of MUC1 on the T-cell surface and the specific form of the glycoprotein expressed.…”

Prevalence and prognostic significance of sMUC‐1 levels in plasma cell dyscrasias

“…In breast cancer patients, sMUC‐1 levels correlate with tumour mass, and CA15·3 assays have been approved by the Federal Drugs Administration, USA, for monitoring disease. Treon et al (2000) have shown a correlation between sMUC‐1 levels, tumour burden and disease activity in patients with plasma cell malignancies, but there are no data concerning sMUC‐1 levels in preneoplastic conditions such as MGUS or their prognostic relevance in terms of survival. In comparison with the normal ranges of the Immulite test (< 51 U/ml), high sMUC‐1 levels were found in 11/89 subjects with MGUS [12·4%; 95% confidence interval (CI): 5·5–19·2], 13/76 with MM (17·1%; 95% CI: 8·6–25·6) and 3/6 with PCL.…”

“…Further analyses are required, but our results suggest that MUC‐1 could have a role in tumour progression; the fact that high levels are very frequently associated with a diagnosis of PCL indicates a possible relationship between them and tumour malignancy (cell proliferation, genetic instability), and this could also explain the association of increased sMUC levels with the subgroup of MM patients with a worse prognosis and higher tumour burden. Some authors have recently demonstrated an inverse correlation between sMUC‐1 levels and IgM anti‐sMUC‐1 in ovarian cancers and plasma cells neoplasms (Richards et al , 1998; Treon et al , 2000), suggesting that MUC1 may have a role as an immunosuppressant agent in tumour progression.…”

Regulated expression of MUC1 epithelial antigen in erythropoiesis

“…Despite the definition of MUC1 as an epithelial tumour antigen, recent findings have shown that non‐epithelial cells can express MUC1 (Brugger et al , 1999). Tumour cells of mesodermal origin show MUC1 expression in lymphoma, myeloma and plasma cell malignancies (Treon et al , 2000a,b;ten Berge et al , 2001; Brossart et al , 2001). MUC1 has also been detected on activated T cells, in monocyte‐derived dendritic cells and it has recently been denominated as CD227 (Agrawal et al , 1998b; McGuckin et al , 2000).…”