Serum Anti-BPAG1 Auto-Antibody Is a Novel Marker for Human Melanoma

Abstract

Malignant melanoma is one of the most aggressive types of tumor. Because malignant melanoma is difficult to treat once it has metastasized, early detection and treatment are essential. The search for reliable biomarkers of early-stage melanoma, therefore, has received much attention. By using a novel method of screening tumor antigens and their auto-antibodies, we identified bullous pemphigoid antigen 1 (BPAG1) as a melanoma antigen recognized by its auto-antibody. BPAG1 is an auto-antigen in the skin disease bullous pemphigoid (BP) and anti-BPAG1 auto-antibodies are detectable in sera from BP patients and are used for BP diagnosis. However, BPAG1 has been viewed as predominantly a keratinocyte-associated protein and a relationship between BPAG1 expression and melanoma has not been previously reported. In the present study, we show that bpag1 is expressed in the mouse F10 melanoma cell line in vitro and F10 melanoma tumors in vivo and that BPAG1 is expressed in human melanoma cell lines (A375 and G361) and normal human melanocytes. Moreover, the levels of anti-BPAG1 auto-antibodies in the sera of melanoma patients were significantly higher than in the sera of healthy volunteers (p<0.01). Furthermore, anti-BPAG1 auto-antibodies were detected in melanoma patients at both early and advanced stages of disease. Here, we report anti-BPAG1 auto-antibodies as a promising marker for the diagnosis of melanoma, and we discuss the significance of the detection of such auto-antibodies in cancer biology and patients.

Human melanomas and ovarian cancers overexpressing mechanical barrier molecule genes lack immune signatures and have increased patient mortality risk

“…Desmosomes are reinforced by armadillo proteins including plakophilin. Expression of desmosomal barrier molecules has been observed in several solid tumors, with mixed prognostic associations 30-37 . In melanoma, elevated levels of the cadherin desmocollin 3 (DSC3) has been associated with increased metastatic risk, but in colon and lung cancer, it has been associated with a better prognosis 31-33 .…”

Serum anti-AEG-1 auto-antibody is a potential novel biomarker for malignant tumors

“…Therefore, serum profiling of circulating auto-antibodies is considered an attractive method in the diagnosis of cancer at early stages. Several markers, such as Her2, BPAG1 and GRP78, have been detected and proposed for immunotherapeutic approaches (7)(8)(9), such as high-titer HER-2/neu protein-specific antibody, which was detected in patients with early stage breast cancer (7). The levels of anti-BPAG1 auto-antibodies were significantly higher in the sera of melanoma patients than in those of the healthy volunteers, and anti-BPAG1 auto-antibodies were detected in melanoma patients at the early and advanced stages of disease (8).…”

Spectraplakin family proteins – cytoskeletal crosslinkers with versatile roles

“…A BPAG1 autoantibody has been identified as a marker for human melanoma (Shimbo et al, 2010). Although BPAG1 was initially found to be expressed in keratinocytes, it is now known to be expressed in many cell types, including melanoma cell lines (AA375 and G361) and tumors, as well as in normal melanocytes (Shimbo et al, 2010).…”

“…Although BPAG1 was initially found to be expressed in keratinocytes, it is now known to be expressed in many cell types, including melanoma cell lines (AA375 and G361) and tumors, as well as in normal melanocytes (Shimbo et al, 2010). However, this raises the question as to whether there are specific isoforms of BPAG1 that are expressed in melanocytes and might be involved in melanoma.…”