IL-24 in regulation of antitumor immune response and in signaling

Abstract

In cancer therapy, cytokines are generally used to increase immunity. Cytokines are either proteins or glycoproteins, which are secreted by immune cells. It is now known that the tumor microenvironment secretes a mixture of cytokines that plays an important role in carcinogenesis. In chronic inflammation, cytokines released at the site of a tumor facilitate tumor growth, instead of promoting antitumor immunity. In 1995, a protein called melanoma differentiation-associated gene-7 (MDA-7), also known as suppressor of tumorigenicity-16 (ST-16), was discovered; it was renamed as interlukine-24 because of its cytokine-like properties and was found to inhibit the growth and proliferation in melanoma cells. The rat counterpart of IL-24 was named as mob-5 or C49a. The murine counterpart was named as FISP. Ectopic expression of MDA-7/IL-24 by means of a replication defective adenovirus (Ad-MDA-7/IL-24) results in growth suppression, inhibits angiogenesis and apoptosis not only in melanoma cells but also in numerous other cancer cell types such as glioblastoma, carcinomas of breast, colon, lung, ovarian and prostate sparing normal epithelial and fibroblasts. Therefore, this article reviews anti-cytokine therapies of MDA-7/IL-24 being pursued in cancer and more details about signaling pathways associated with MDA-7/IL-24 in cancer. © 2009 Springer-Verlag New York.