153 CARBONIC ANHYDRASE XII: POTENTIAL ROLE IN LYMPHATIC METASTASES OF RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research I1 Apr 2012153 CARBONIC ANHYDRASE XII: POTENTIAL ROLE IN LYMPHATIC METASTASES OF RENAL CELL CARCINOMA Nnenaya Agochukwu, Kiranpreet Khurana, Eric Kauffman, Brian Shuch, Vladimir Valera, Youfeng Yang, W. Marston Linehan, and Gennady Bratslavsky Nnenaya AgochukwuNnenaya Agochukwu Bethesda, MD More articles by this author , Kiranpreet KhuranaKiranpreet Khurana Cleveland, OH More articles by this author , Eric KauffmanEric Kauffman Bethesda, MD More articles by this author , Brian ShuchBrian Shuch Bethesda, MD More articles by this author , Vladimir ValeraVladimir Valera Bethesda, MD More articles by this author , Youfeng YangYoufeng Yang Bethesda, MD More articles by this author , W. Marston LinehanW. Marston Linehan Bethesda, MD More articles by this author , and Gennady BratslavskyGennady Bratslavsky Syracuse, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.203AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Metastasis in renal cell carcinoma (RCC) is a major predictor of survival, yet little is known about metastasis of RCC to the lymph nodes. Using matched pairs of cell lines derived from patients with a primary tumor of RCC origin and sites of lymph nodal metastasis also of RCC origin, we sought to investigate the potential differences between the lymph node metastasic site and the primary site in tumor cell lines derived from the same patients. METHODS The cell lines used for this analysis were obtained from the Urologic Oncology Branch of the NCI cell repository and included 3 pairs with the von Hippel- Lindau (VHL) mutation and 1 pair with a mutation in the Transcription factor E3 (TFE3) gene. Each pair represents one patient. Sequencing and fingerprinting were done to confirm that the origin of each pair of cell lines were from the same patient. Gene expression microarrays using an affymetrix platform followed by Real Time Polymerase Chain Reaction (RT-PCR) were done to confirm the differentially expressed genes. Western blot was subsequently done to confirm RT-PCR findings using a monocolonal antibody. RESULTS Sequencing and fingerprinting confirmed that the matched pair cell lines were from the same patient. Microarray gene expression array demonstrated differential expression of several genes with Carbonic Anhydrase XII (CAXII) overexpression in metastatic cell lines in 3 different probes with up to 4 fold difference. RT-PCR confirmed our microarray findings with increased expression of CAXII in the cell lines derived from sites of lymph nodal metastases. Western blot analysis confirmed increased expression of the CAXII protein for the metastatic cell lines when compared to cell lines derived from the primary tumors. CONCLUSIONS The present results demonstrate that CAXII has increased expression in metastatic RCC as compared to primary RCC from the matched cell lines. Such findings may be due to adaptation to the lymph node environment and provide an explanation for the mechanism that metastatic cells employ to survive in the lymph environment thereby avoiding the recognition or destruction by the immune cells. Further assays will be performed to better elucidate the role of CAXII in lymph node metastases. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e63 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nnenaya Agochukwu Bethesda, MD More articles by this author Kiranpreet Khurana Cleveland, OH More articles by this author Eric Kauffman Bethesda, MD More articles by this author Brian Shuch Bethesda, MD More articles by this author Vladimir Valera Bethesda, MD More articles by this author Youfeng Yang Bethesda, MD More articles by this author W. Marston Linehan Bethesda, MD More articles by this author Gennady Bratslavsky Syracuse, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...