IL-4-mediated drug resistance in colon cancer stem cells

Cancer stem cells are defined as cells able to both extensively self-renew and differentiate into progenitors. Cancer stem cells are thus likely to be responsible for maintaining or spreading a cancer, and may be the most relevant targets for cancer therapy. The CD133 glycoprotein was recently described as a reliable cancer stem-like cell marker in colon carcinoma. CD133(+) cells are both necessary and sufficient to initiate tumor growth in animal models. The CD133(+) cell population and spheroid cultures contain cells expressing the stem cell marker Musashi-1 which is involved in maintenance of stem cell fate in several tissues and importantly, this expression is maintained in stem-like cells derived from xenografted tumors. Here we discuss the potential use of the CD133 antigen in concert with Musashi-1 as markers to identify the colon cancer stem cell population. Since the upregulation of IL-4 cytokine was recently demonstrated to constitute an important mechanism that protects the tumorigenic CD133(+) cells from apoptosis, the potential benefits of standard chemotherapeutic treatments in combination with IL-4 inhibitors in the context of human colon carcinoma, are also discussed.