CD55 as a marker of Cancer Stem Cells

Osaka, Japan - The search for tumor stem cells has revealed numerous markers that are present on non-tumor stem cells as markers of tumor stem cells. For example, the recent discovery that CD133 is found on colon cancer stem cells should not be a surprise, since this marker is also found on other types of stem cells. What SHOULD BE A SURPRISE is the recent publication by Xu et al (High tolerance to apoptotic stimuli induced by serum depletion and ceramide in side-population cells: High expression of CD55 as a novel character for side-population. Exp Cell Res. 2007 Mar 15;) demonstrating that side population cancer stem cells express the marker CD55. CD55 is a protein that inhibits ability of complement to activate and kill cells. CD55 therefore may not only be a good marker of tumor stem cells, but also a therapeutic target since it may play a role in tumor stem cells escaping complement mediated killing. Others have previously demonstrated that "natural antibodies" exist to tumor cells (Brandlein S, et al. PAM-1, a natural human IgM antibody as new tool for detection of breast and prostate precursors. Hum Antibodies. 2004;13(4):97-104), therefore it will be interesting to examine whether tumor stem cells ALSO POSSESS OTHER PROPERTIES THAT ALLOW ESCAPE FROM IMMUNE ATTACK. We predict that as this field advances, preferential production of IL-10, suppression of HLA, and upregulation of immune suppressive molecules will be found preferentially on tumor stem cells.

In terms of CD55, it may be interesting to note that certain groups are inducing immune responses to CD55 in patients with colorectal cancer by administration of anti-idiotypic CD55 in the presence of BCG (Ullenhag et al.  A neoadjuvant/adjuvant randomized trial of colorectal cancer patients vaccinated with an anti-idiotypic antibody, 105AD7, mimicking CD55. Clinical Cancer Research. 2006 Dec 15;12(24):7389-96).  Further hints of the immune suppressive activity of CD55 include the US patent # 6,916,654 which covers a "Universal Donor" cell and one of the activities of the cell is expression of CD55.