Retinoblastoma protein activation of interleukin 8 expression inhibits tumor cell survival in nude mice.
Loss of 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.
Zhang
H
H
Department of Pathology and Laboratory Medicine, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612, USA.
Wei
S
S
Sun
J
J
Coppola
D
D
Zhong
B
B
Wu
G D
GD
Goodwin
B
B
Sebti
S
S
Djeu
J Y
JY
Blanck
G
G
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental; D009504:Neutrophils / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D013997:Time Factors
D017077:Culture Media, Conditioned; D007074:Immunoglobulin G; D016209:Interleukin-8; D016160:Retinoblastoma Protein