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 tumour 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.
Todaro
Matilde
M
Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, Palermo, Italy.
Perez Alea
Mileidys
M
Scopelliti
Alessandro
A
Medema
Jan Paul
JP
Stassi
Giorgio
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000502:physiology*
D000970:Antineoplastic Agents; D015847:Interleukin-4