Article

Expression of CD175 (Tn), CD175s (sialosyl-Tn) and CD176 (Thomsen-Friedenreich antigen) on malignant human hematopoietic cells

Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany.
International Journal of Cancer (Impact Factor: 5.01). 07/2008; 123(1):89-99. DOI: 10.1002/ijc.23493
Source: PubMed

ABSTRACT The expression of the histo-blood group carbohydrate structures T-nouvelle (Tn, CD175), sialylated Tn (CD175s) and the Thomsen-Friedenreich disaccharide (TF, CD176) on human leukemia cell lines was analyzed by their reactivity with specific monoclonal antibodies in flow cytometry, immunohistology and immunoprecipitation. Expression of sialylated CD176 was evaluated by comparative immunostaining with anti-CD176 antibodies before and after sialidase treatment. While only few cell lines expressed unmasked CD176, sialylated CD176 was present on all hematopoietic cell lines and native lymphocytes examined. CD175 and CD175s are preferentially expressed on erythroblastic leukemia cell lines. CD175s expression in these cells is consistent with the transcription of the gene encoding the key enzyme alpha2,6-sialyltransferase (hST6GalNAc1). The staining intensity was reduced after methanol pretreatment of cells, indicating that these glycans are partially expressed as constituents of glycosphingolipids. Immunoprecipitation and subsequent Western blotting revealed a series of distinct high molecular glycoproteins as carriers for these carbohydrate antigens. CD34 was identified as major carrier of CD176 by immunoprecipitation and microsequencing on a KG-1 subline enriched for CD176 expression. Incubation of several CD176-positive cell lines with anti-CD176 antibodies induced apoptosis of these cells, an effect not observed with anti-CD175/CD175s antibodies. Since the presence of naturally occurring anti-CD176 antibodies may represent a mechanism of immunosurveillance against CD176-positive tumor cells, we propose that sialylation of surface-expressed CD176--among other functions--protects against apoptosis.

Full-text

Available from: Reinhard Schwartz-Albiez, Oct 13, 2014
0 Followers
 · 
138 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The incidence of thyroid cancer has appeared as an increasing trend globally, especially in Asian countries. In this study, the expression of mucin-1 (MUC1) and Thomsen-Friedenreich antigen, Galβ1-3GalNAcα1-R (CD176) was investigated by immunohistochemistry in papillary thyroid carcinomas (PTCs), which accounts for approximately 80 % of all thyroid cancer. We found that 78 % of PTC overexpressed MUC1. Importantly, we observed firstly that CD176 was expressed in 63 % of PTC, but was faintly or not expressed in normal thyroid tissues and benign thyroid disease tissues, indicating that CD176 is also a tumour-associated antigen for PTCs. Moreover, expression of CD176 was strongly correlated with MUC1 by immunohistochemical staining in PTCs. Furthermore, we used the immunochemical method to confirm that MUC1 is a common and main carrier of CD176 in PTCs. Our data demonstrated that MUC1 and CD176 might be promising biomarkers for thyroid cancer.
    Endocrine Pathology 01/2015; 26(1). DOI:10.1007/s12022-015-9356-9 · 1.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent reports suggest a possible role of extracellular (MUC1N) and transmembrane (MUC1C) subunits of Mucin 1 (MUC1) in pathogenesis of multiple myeloma (MM). Nuclear translocation of MUC1C is involved in activation of various oncogenic signalling pathways and both MUC1 subunits are potential therapeutic target. We aimed at performing a comprehensive expression analysis of the MUC1 subunits in plasma cell dyscrasias. Immunohistochemistry with monoclonal antibodies against MUC1N (EMA and 5E10), tumour associated-glycoforms of MUC1N (5E5) and MUC1C subunit were applied on a series of biopsies from normal controls (n=10) and plasma cell dyscrasias (n=121). Clonal plasma cells showed reduced MUC1N expression, and the 5E5 MUC1N epitope was only expressed in neoplastic plasma cells. Nuclear localization of MUC1C was equally frequent in all diseases stages and did not differ from the control cases. Loss of both MUC1 subunits in MM (n=12) was associated with significantly shorter overall survival and was more frequent in pre-treated MM samples. Our findings indicate that aberrant glycosylation of MUC1 is an early event in the pathogenesis of MM. In contrast, MUC1C nuclear localization is not likely to be a driver of tumour progression. This article is protected by copyright. All rights reserved.
    Histopathology 11/2013; 64(6). DOI:10.1111/his.12330 · 3.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: CD176 (Thomsen-Friedenreich antigen) is a tumor-associated carbohydrate structure. CD176 is expressed at the surface of human leukemic cells but is almost absent in normal and benign adult human tissues. Therefore, CD176 could be a promising target for antitumor immunotherapy. In the present study, pre-immunization with asialoglycophorin A (containing the CD176 oligosaccharide chains) was able to significantly improve the survival time of mice carrying CD176+ leukemia as compared to the control mice without the immunization. Furthermore, the passive transfer of CD176 antiserum which reacted only with the tumor-associated CD176 in cancer cells, was able to effectively prolong the survival time of CD176+ leukemia mice. In particular, the CD176 antiserum treatment could inhibit the growth and spreading of CD176+ leukemic cells in bone marrow, spleen, liver, and lung as evidenced by histopathological examination. CD176 antiserum could induce the apoptosis of CD176+ leukemic cells in vivo in a manner as previously observed in vitro. The data provided strong evidence that both CD176 antigen-based active immunotherapy and CD176 antibody-based passive immunotherapy lead to a therapeutic response in CD176+ leukemia mice. Therefore, both CD176 vaccine and CD176 antibody drug may be beneficial for the treatment of CD176+ leukemia patients.
    Oncology Reports 07/2013; 30(4). DOI:10.3892/or.2013.2639 · 2.19 Impact Factor