WASHINGTON, DC USA (UroToday.com) - This group identified 234 candidate suppressor genes and focused on RhoGDI2.
They experimentally demonstrated that it is a metastasis suppressor. They performed expression profiling in response to GD12 to pick candidates relevant to human cancer. Targets of RhoGDI2 included endothelin-1 (ET-1) and its receptors. They found that ET-1 did not affect human bladder cancer primary tumor growth but did affect growth at the metastatic site. ETA receptor blockade inhibited metastasis while ETB receptor inhibition did not.
They developed a 2-step hypothesis. In step one tumor ET-1 chemo-attracts macrophages to the lung, and in step two macrophages facilitate metastatic colonization. They found that a linear correlation between metastatic colonization and the lung inflammatory response. Inhibition of ET-1 on early metastatic colonization revealed that it had no effect on the tumor cell colonization but did inhibit the inflammatory response. Thus, he concluded that GDI2 is a lung metastatic suppressor gene that affects tumor ET-1 expression. ET-1 induces macrophage accumulation and cytokine secretion that then promotes tumor colonization in the metastatic site.
Presented by Dan Theodorescu, MD, PhD at the Society for Basic Urologic Research (SBUR)/Society of Urologic Oncology (SUO) joint meeting during the American Urological Association (AUA) Annual Meeting - May 14 - 19, 2011 - Walter E. Washington Convention Center, Washington, DC USA
Reported for UroToday by Christopher P. Evans, MD, FACS, Professor and Chairman, Department of Urology, University of California, Davis, School of Medicine.
View Full AUA 2011 Meeting Coverage