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Retinoblastoma Protein Activation of Interleukin 8 Expression Inhibits Tumor Cell Survival in Nude Mice¹

Departments of Pathology and Laboratory Medicine [H. Z., D. C., G. B.], and Biochemistry and Molecular Biology [S. W., J. S., B. Z., B. G., S. S., J. Y. D., G. B.], H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612 [S. W., J. S., D. C., B. Z., S. S., J. Y. D., G. B.]; and Department of Internal Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 [G. D. W.]

Abstract

Lossof retinoblastoma protein (Rb) has been implicated in the formation of a variety of human malignancies. Restoration of Rb expression in the cell lines representing these tumors eliminates or significantly reduces tumorigenicity in nude mice, but the mechanism for this Rb effect is unknown. Results from this study indicated that Rb expression reduced tumor cell survival in nude mice by dramatically enhancing interleukin 8 (IL-8) secretion. IL-8 secreted by the Rb-transformed cells attracted neutrophils in vitro and tumor-infiltrating neutrophils in vivo, which is consistent with the Rb-mediated tumor regression being dependent on IL-8. The apparent, contradictory roles of IL-8 as a protumorigenic and antitumorigenic cytokine are discussed.