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Published on: January 14, 2011
Retinoblastoma protein activation of interleukin 8 expression inhibits tumor cell survival in nude mice
1Department of Pathology and Laboratory Medicine, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612, USA.
Abstract:
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.
Insights
Restoring retinoblastoma protein (Rb) expression in cancer cells significantly reduced tumor growth in mice by increasing interleukin-8 (IL-8) secretion, which attracted neutrophils to the tumor site.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Loss of retinoblastoma protein (Rb) is linked to various human cancers.
- Restoring Rb expression reduces tumor formation but the mechanism remains unclear.
Purpose of the Study:
- To investigate the mechanism by which retinoblastoma protein (Rb) suppresses tumor cell survival.
- To explore the role of interleukin-8 (IL-8) in Rb-mediated tumor regression.
Main Methods:
- Utilized cell lines with restored Rb expression.
- Assessed tumor cell survival and tumorigenicity in nude mice.
- Measured interleukin-8 (IL-8) secretion levels.
- Analyzed neutrophil recruitment in vitro and in vivo.
Main Results:
- Restored Rb expression significantly reduced tumor cell survival in vivo.
- Rb expression dramatically enhanced IL-8 secretion by tumor cells.
- Secreted IL-8 attracted neutrophils, correlating with Rb-mediated tumor regression.
Conclusions:
- Rb-mediated tumor regression is dependent on enhanced IL-8 secretion and subsequent neutrophil infiltration.
- Highlights the complex, dual role of IL-8 in cancer, acting as both a pro- and anti-tumorigenic cytokine.
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