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.
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