Mechanisms of the apoptosis induced by CD176 antibody in human leukemic cells

  • Authors:
    • Bin Yi
    • Min Zhang
    • Reinhard Schwartz-Albiez
    • Yi Cao
  • View Affiliations

  • Published online on: March 30, 2011     https://doi.org/10.3892/ijo.2011.992
  • Pages: 1565-1573
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Abstract

CD176 (Thomsen-Friedenreich antigen) is a tumor-associated carbohydrate structure. In a previous study, we observed that the anti-CD176 antibody can induce the apop­tosis of CD176-positive leukemic cells. In this study, we investigated the mechanisms of apoptosis induced by the CD176 antibody. We found that CD95 (FAS, APO-1) and the death receptor 4 (DR4) (TRAIL-R1) are co-expressed with CD176 on the surface of defined leukemic cells as observed by confocal microscopy and flow cytometry analyses. Further­more, CD95, CD45, CD43 and DR4 are carrier proteins of CD176 in hematopoietic cells recognized by means of sandwich solid-phase enzyme linked immunosorbent assay and co-immunoprecipitation. As shown by microarray analysis, 20 genes which are directly related to the execution, induction or positive regulation of apoptosis, were up-regulated after CD176 antibody treatment of the KG1 cell line. Nine differ­entially expressed genes observed in the microarray analysis were verified by quantitative real-time polymerase chain reaction in the KG1 and MT4 cell lines. Six genes (DAXX, CASP3, CHUK, RIPK2, NFKBIA and DFFA) out of these nine are involved in five apoptotic pathways: The CD95 signaling pathway, the DR3 and DR4/5 death receptor pathway, caspase cascade in apoptosis, the mitochondrial signaling pathway, and apoptotic DNA fragmentation and tissue homeo­stasis. Thus, we hypothesized that the CD176 antibody binds to the CD176 carbohydrate structure present on apoptosis-associated glycoproteins, such as CD95 and DR4 at the cellular surface, which activates apoptotic pathways, and consequently results in the apoptosis of CD176-positive cells. CD176 is expressed at the surface of human leukemic cells, but is almost absent in normal and benign adult human tissues. Thus, CD176 could be a promising target for anti-tumor therapy based on the induction of tumor-specific apoptosis.

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June 2011
Volume 38 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yi B, Zhang M, Schwartz-Albiez R and Cao Y: Mechanisms of the apoptosis induced by CD176 antibody in human leukemic cells. Int J Oncol 38: 1565-1573, 2011
APA
Yi, B., Zhang, M., Schwartz-Albiez, R., & Cao, Y. (2011). Mechanisms of the apoptosis induced by CD176 antibody in human leukemic cells. International Journal of Oncology, 38, 1565-1573. https://doi.org/10.3892/ijo.2011.992
MLA
Yi, B., Zhang, M., Schwartz-Albiez, R., Cao, Y."Mechanisms of the apoptosis induced by CD176 antibody in human leukemic cells". International Journal of Oncology 38.6 (2011): 1565-1573.
Chicago
Yi, B., Zhang, M., Schwartz-Albiez, R., Cao, Y."Mechanisms of the apoptosis induced by CD176 antibody in human leukemic cells". International Journal of Oncology 38, no. 6 (2011): 1565-1573. https://doi.org/10.3892/ijo.2011.992