Possible Roles of Interleukin-4 and -13 and Their Receptors in Gastric and Colon Cancer

Abstract

Interleukin (IL)-4 and -13 are structurally and functionally related cytokines sharing common receptor subunits. They regulate immune responses and, moreover, are involved in the pathogenesis of a variety of human neoplasms. Three different receptors have been described for IL-4, but only IL-4 receptor type II (IL-4Rα/IL-13Rα1) is expressed in solid tumors. While IL-13 can also bind to three different receptors, IL-13 receptor type I (IL-4Rα/IL-13Rα1/IL-13Rα2) and type II (IL-4Rα/IL-13Rα1) are expressed in solid tumors. After receptor binding, IL-4 and IL-13 can mediate tumor cell proliferation, survival, and metastasis in gastric or colon cancer. This review summarizes the results about the role of IL-4/IL-13 and their receptors in gastric and colon cancer.

Keywords: gastrointestinal cancer; interleukin-13; interleukin-13 receptor; interleukin-4; interleukin-4 receptor.

Figure 1

Receptor types and signal transduction of IL-4R and IL-13R. There are three different kinds of IL-4 receptors. IL-4 binds to the IL-4Rα chain, then recruits the IL-2Rγ-common (γc) chain (type I IL-4R) or the IL-13Rα1 chain (type II IL-4R) to form a receptor complex that can initiate signal transduction. The type III IL-4R consists of all three chains. IL-13 also have three different receptors. IL-13 receptor type I (IL-4Rα/IL-13Rα1/IL-13Rα2) and type II (IL-4Rα/IL-13Rα1) are expressed in solid tumors, while type III (IL-4Rα/IL-13Rα1/γc) is expressed in hemocytes only. IL-13 binds IL-13Rα1 with a low affinity and complexes with the IL-4Rα (type II receptor). IL-13 binds to the IL-13Rα2 with a high affinity. IL-13 can bind to a soluble IL-13Rα2 receptor, which has no downstream signaling, or bind to transmembrane IL-13Rα2 and activate AP-1. Figure sketch adapted from reference [27].