Cancer progression is dependent on the ability of tumor cells to interact with and favorably influence their environment. For instance, if a tumor is going expand, it is absolutely critical that new blood vessels are formed so that an adequate blood supply is in place to feed the growing tissue. A new research study published in the November issue of Cancer Cell demonstrates that a cytokine, a chemical signal that stimulates inflammation, plays a critical role in the initiation of new vasculature formation required to promote tumor progression.
Previous research has suggested that there may be a link between cancer-associated angiogenesis and inflammation. The protooncogene Ras has also been implicated in tumor-driven blood vessel generation. Ras is abnormally activated in nearly one quarter of all human cancers and is involved in many aspects of tumor progression, including interactions between tumor cells and the surrounding environment. However, the mechanisms that underlie these interactions are unclear.
Dr. Dafna Bar-Sagi from the Department of Molecular Genetics and Microbiology at the State University of New York at Stony Brook examined whether Ras-mediated induction of the inflammatory mediator CXCL-8 was required for tumor growth and angiogenesis in a mouse model. The researchers found that CXCL-8 production was required for Ras-stimulated tumor inflammation, vascularization, and growth. In addition, inhibition of CXCL-8 function in tumors expressing Ras led to a marked decrease in tumor angiogenesis.
Molecules that modulate CXCL-8 expression are known targets of the Ras signaling pathway, establishing a physiological link between these signaling molecules. The researchers conclude that in response to Ras activation, proinflammatory cytokines such as CXCL-8 may recruit immune cells and endothelial cells to tumor sites, representing a new mechanism for cancer-driven blood vessel generation. According to Dr. Bar-Sagi, "Our findings underscore the contribution of dysregulated CXCL-8 expression to the process of Ras-mediated tumorigenesis and suggest that this chemokine and its receptors may serve as attractive anticancer therapeutic targets."
Anke Sparmann and Dafna Bar-Sagi: "Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis"
Publishing in Cancer Cell, Volume 6, Number 5, November 2004, pages 447-458.