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Crucial Role of Interleukin-4 in the Survival of Colon Cancer Stem Cells

¹ Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, Palermo, Italy and ² Laboratory for Experimental Oncology and Radiobiology (LEXOR), Academic Medical Center, Amsterdam, the Netherlands

Requests for reprints: Giorgio Stassi, Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, 90127 Palermo, Italy. Phone: 39-91655-3211; Fax: 39-91655-3238; E-mail: gstassi{at}tiscali.it or J.P. Medema, E-mail: J.P.Medema{at}amc.uva.nl.

Key Words: cancer stem cells • colon cancer • IL-4

Colon tumors may be maintained by a rare fraction of cancer stem-like cells (CSC) that express the cell surface marker CD133. Self-renewing CSCs exhibit relatively greater resistance to clinical cytotoxic therapies and recent work suggests that this resistance may be mediated in part by an autocrine response to the immune cytokine interleukin 4 (IL-4). Blocking IL-4 signaling can sensitize CSCs to apoptotic stimuli and increase the in vivo efficacy of cytotoxic therapy. These findings suggest that inhibitors of IL-4 signaling may offer a new therapeutic tool in colon carcinoma. [Cancer Res 2008;68(11):4022–5]