Cancer antigens are expressed in a carcinogen-transformed Bloom syndrome B-lymphoblastoid cell line.

Abstract

We have cloned malignant cells carrying specific antigens associated with ovarian cancer (OVC) and malignant lymphoma (ML) from BS-SHI.4M cells, a line derived from a 1-methyl-3-nitro-1-nitrosoguanidine-treated Blymphoblastoid cell line isolated from a patient with Bloom syndrome. Since BS-SHI-4M cells react with sera from various individual cancer patients at relatively low frequencies (2-9%), as detected by an indirect immunofluorescence technique, cell clones that specifically react with sera from patients with OVC and ML were separated by the "panning" method in which polystyrene dishes were coated with sera from OVC and ML patients and cells with the corresponding antigens bound to the dishes. Subsequent cloning by limiting dilution provided cell clones highly enriched for OVC-and ML-associated antigens. Karyotype analyses revealed that cell clones with OVC and ML antigens had common marker chromosomes, der(14)t(14;14) (pll;qll),t(6;?)(p25;?) and t(9;?)(q34;?), besides t(17;?) (q25;?) found in the OVC-antigen-positive clones and t(5;?) (pl3;?),t(7;?)(q36;?) found in the ML-antigen-positive clones. Interestingly, in cell clones with a strong OVC antigen response, the distal part of the Y chromosome (Yqll) was missing in 100% of the cells. Therefore the cell line BS-SE114M appears to be a reservoir of cell clones each of which carries a specific tumor antigen and thus provides a potential tool for rapid serological diagnosis of cancer.Bloom syndrome (BS) is an autosomal-recessive genetic disorder characterized by stunted growth, sensitivity to sunlight, immunodeficiency, and marked predisposition to various types of cancer (1). BS differs distinctly from certain other recessive genetic disorders that are also characterized by chromosome instability and cancer proneness in that it is not predisposed to a particular type of cancer, as seen in xeroderma pigmentosum (a predisposition to cancer of sunexposed tissues), Fanconi anemia (a predisposition to leukemia and hepatic cancer), and ataxia telangiectasia (a predisposition to lymphoma) (1). The striking feature of BS is that it predisposes patients to diverse types of cancers. This suggests that in BS the types of cancer are basically of the same kind as in normal persons but that the process of carcinogenesis is accelerated. Therefore, the elucidation of the mechanism(s) of carcinogenesis in BS would be of great value in the study of human carcinogenesis in general. B-lymphoblastoid cell lines (B-LCLs) have been established from BS patients that are highly susceptible to malignant transformation after carcinogen treatments, as shown by tumor production in nude mice and cell growth in agar (2, 3). When BS-SHI-4 cells, a BS B-LCL, were treated with a carcinogen and cultured in vitro, the resulting cells (BS-SHI-4M) carried cancer antigens that reacted with the antibodies present in the sera of patients with various malignancies [malignant lymphoma (ML), ovarian cancer (OVC), stomach cancer (ST), or hepatic cancer (HC)]. We have developed a simple method ...

CD133/CD166/Ki-67 Triple Immunouorescence Assessment for Putative Cancer Stem Cells in Colon Carcinoma*

“…Over the past decade, alterations in expression of CD166 have been reported to correlate with an aggressive disease phenotype in a variety of cancers [26][27][28][29][30]. However, inconsistent data also exist regarding the prognostic signi cance of CD166 expression in CRC [19,[31][32][33][34].…”