616 CHARACTERISTICS OF PRIMARY TUMOR MAY PREDICT BONE METASTASIS IN RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research (IV)1 Apr 2013616 CHARACTERISTICS OF PRIMARY TUMOR MAY PREDICT BONE METASTASIS IN RENAL CELL CARCINOMA Elke Schneider, Tobias Haber, Frederik C. Roos, Dirk Prawitt, Kerstin Junker, Christian Hampel, Joachim W. Thueroff, and Walburgis Brenner Elke SchneiderElke Schneider Mainz, Germany More articles by this author , Tobias HaberTobias Haber Mainz, Germany More articles by this author , Frederik C. RoosFrederik C. Roos Mainz, Germany More articles by this author , Dirk PrawittDirk Prawitt Mainz, Germany More articles by this author , Kerstin JunkerKerstin Junker Homburg/Saar, Germany More articles by this author , Christian HampelChristian Hampel Mainz, Germany More articles by this author , Joachim W. ThueroffJoachim W. Thueroff Mainz, Germany More articles by this author , and Walburgis BrennerWalburgis Brenner Mainz, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.167AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The poor prognosis of renal cell carcinoma (RCC) is caused by a high risk of metastasis. 30% of RCC patients develop bone metastases during the course of disease. A method of predicting bone metastasis would benefit the otherwise poor outcome of this patient group. The aim of this study was to elucidate the mechanisms that lead to organ-specific metastasis of RCC in bones and thereby predict bone metastasis. METHODS In 30 RCC tissue specimens and 9 RCC primary cell lines collected from patients who had developed no metastases, lung or bone metastases within 5 years after nephrectomy (each 10 RCC tissue specimens, each 3 RCC cell lines) expression and/or activity of 46 cellular signaling molecules were quantified by phospho-kinase array and Western blot analyses. To investigate metastatic behavior, migration of the primary RCC cells was analysed in a Boyden chamber with 10 μg/ml fibronectin as chemotaxin, and adhesion to extracellular matrix compounds fibronectin, collagen I and IV was determined after cell staining with crystal violet. RESULTS In RCC tissue specimens and primary cells from patients who developed bone metastases, a higher expression of α5 integrins, higher activity of Akt and FAK and a lower expression of PTEN were detected, compared to those from patients without or with lung metastases. These results show an enhanced chemotactic migration (13-fold) of bone metastatic RCC cells and adhesion to fibronectin (6-fold) or collagen type I (8-fold) - both components of the bone matrix. CONCLUSIONS Specific characteristics such as expression and activity of cell signaling mediators and cellular behavior of the primary tumor determine the location of subsequent metastasis in RCC and could be used as a prognostic marker for bone metastasis. This should be considered during follow-up care. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e252 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elke Schneider Mainz, Germany More articles by this author Tobias Haber Mainz, Germany More articles by this author Frederik C. Roos Mainz, Germany More articles by this author Dirk Prawitt Mainz, Germany More articles by this author Kerstin Junker Homburg/Saar, Germany More articles by this author Christian Hampel Mainz, Germany More articles by this author Joachim W. Thueroff Mainz, Germany More articles by this author Walburgis Brenner Mainz, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...