NEW YORK (Reuters Health) - Interleukin (IL)-8 expression induced by the Ras oncogene is required for tumor-associated inflammation and neovascularization in a nude mouse xenograft model, according to a report in the November issue of Cancer Cell.
Nevertheless, the therapeutic implications of these findings are uncertain, investigator Dr. Dafna Bar-Sagi told Reuters Health. “Systemic inhibition of IL-8 will undoubtedly compromise normal immune function. However, targeted ablation of IL-8 function at the tumor site should be rather harmless and of potential therapeutic benefit.”
Ras oncogenes clearly promote cellular transformation, the authors point out. However, how Ras signaling influences interactions between tumor cells and the host environment remains unclear.
Drs. Bar-Sagi and Anke Sparmann from the State University of New York at Stony Brook, found that Ras at near-physiological and supraphysiological levels significantly increased the expression of IL-8 in HeLa cells, lung carcinoma cells, and normal, spontaneously immortalized human lumenal mammary epithelial cells.
In the mouse xenograft model, inhibition of IL-8 curtailed tumor growth not by influencing neoplastic cell proliferation but by increasing tumor cell death and reducing tumor vascularization.
By analyzing the neoplastic tissue, the investigators were able to demonstrate that Ras-induced IL-8 is essential for the recruitment of endothelial cells to the tumor site and that the IL-8-induced inflammatory response is required for neovascularization of Ras-expressing tumors.
Collectively, the researchers conclude, “our data identify a novel mechanism by which the Ras oncogene can elicit a stromal response that fosters cancer progression.”
Source: Cancer Cell 2004;6:447-458. [ Google search on this article ]
MeSH Headings:Breast Neoplasms: Neoplasms: Neoplasms by Site: Genes, ras: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
