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

Cancer stem cells are defined as cells able to both extensively selfrenewand differentiate into progenitors. Cancer stem cells are thuslikely to be responsible for maintaining or spreading a cancer, andmay be the most relevant targets for cancer therapy. The CD133glycoprotein was recently described as a reliable cancer stem-like cellmarker in colon carcinoma. CD133+ cells are both necessary andsufficient to initiate tumor growth in animal models. The CD133+cell population and spheroid cultures contain cells expressing the stemcell marker Musashi-1 which is involved in maintenance of stem cellfate in several tissues and importantly, this expression is maintainedin stem-like cells derived from xenografted tumors. Here we discussthe potential use of the CD133 antigen in concert with Musashi-1 asmarkers to identify the colon cancer stem cell population. Since theupregulation of IL-4 cytokine was recently demonstrated to constitutean important mechanism that protects the tumorigenic CD133+cells from apoptosis, the potential benefits of standard chemotherapeutictreatments in combination with IL-4 inhibitors in the contextof human colon carcinoma, are also discussed.