Stage-specific embryonic antigen-4 as a potential therapeutic target in glioblastoma multiforme and other cancers

Abstract

Significance Glioblastoma multiforme (GBM) is a deadly brain tumor. More than 50% of patients who suffer from GBM die within 15 mo even received all possible medical treatment. In this study we report that the glycolipid stage-specific embryonic antigen-4 (SSEA-4) is highly expressed on the surface of both GBM cells and GBM specimens. We further demonstrate that the growth of GBM tumor is inhibited when anti–SSEA-4 antibody is administered to experimental mice, suggesting a research proof of concept for the treatment GBM and other SSEA-4 + cancers.

Stage-specific embryonic antigen-3 (SSEA-3) and β3GalT5 are cancer specific and significant markers for breast cancer stem cells

“…Nevertheless, it appears that, unlike other tumor-associated glycolipids, these three globo-series glycans are cancer specific and could be considered as nonself epitopes for vaccine development. These findings are further supported by the study of antibodies designed to target the globo-series glycans (13)(14)(15)(16)(17)(18), and by the development of globo-H cancer vaccines (19), especially the one in the late-stage clinical trials for the treatment of metastatic breast cancer (28).…”

“…In our previous study, the globo-series glycans SSEA-3 (Gb5), SSEA-4 (sialyl-Gb5), and globo-H (fucosyl-Gb5) are found exclusively on the cell surface of many cancers, including breast cancer and BCSCs (16)(17)(18). We also reported that BCSCs carrying either ESA hi PROCR hi or CD44 + CD24 -/lo showed high expression of these globo-series epitopes (19).…”

Glycolipid GD3 and GD3 synthase are key drivers for glioblastoma stem cells and tumorigenicity

“…We previously showed that the globoseries glycolipids SSEA3 and SSEA4 are highly expressed on GBM cells and that an anti-SSEA4 antibody was effective against GBM (21). As a tumorassociated antigen, GD3 has been an attractive target in immunotherapy (43).…”

“…However, none of these protein markers could be used specifically to identify GSCs, and no study was reported with respect to glycans as potential markers, although glycan biosynthesis involves multiple genes and it is possible to create different structures in cancer progression. It is noted that ganglioside D2 (GD2) and ganglioside D3 (GD3) were found on the surface of neural stem cells (NSCs) and that stage-specific embryonic antigen 3 (SSEA3) and SSEA4 were found on embryonic stem cells and cancer cells (19)(20)(21), but there is no glycan marker found on the surface of GSCs.…”

The DLK1-MEG3 locus in malignant cells of proposed primordial germ cell origins.

“…These CSC subpopulations are often identified based on their expression of certain surface antigens which also exist on normal stem cell populations, including SSEA4, CD133, and DLK1 [11,[67][68][69]. However, several studies have challenged the nature of true CSCs within tumors by providing evidence that these CSC-like subpopulations of cells dynamically express CSC-associated antigens [70,71].…”