MP36-07 ROLE OF ADIPOSE TISSUE IN BLADDER CANCER PROGRESSION

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research I1 Apr 2015MP36-07 ROLE OF ADIPOSE TISSUE IN BLADDER CANCER PROGRESSION Nisha Hariharan, Teresa Johnson-Pais, Robert Svatek, Keith Ashcraft, and Robin Leach Nisha HariharanNisha Hariharan More articles by this author , Teresa Johnson-PaisTeresa Johnson-Pais More articles by this author , Robert SvatekRobert Svatek More articles by this author , Keith AshcraftKeith Ashcraft More articles by this author , and Robin LeachRobin Leach More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.735AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Obesity is associated with an increased risk of disease recurrence in patients with bladder cancer. One potential explanation is that adipose tissue surrounding the bladder may secrete tumor-promoting factors as this has been shown in other solid malignancies. The objective of our study is to elucidate the paracrine interactions between adipose tissue and surrounding bladder tumor as a potential contributor to disease progression. Hence, we characterized potential secreted pro-tumor factors in adipose tissue of obese and non-obese muscle-invasive bladder cancer (MIBC) patients. METHODS Adipose tissue in the abdominal subcutaneous space and surrounding the urinary bladder, urachus, and prostate was collected from normal weight [Body Mass Index (BMI) under 25 kg/m2, n=5], overweight (BMI 25 to 29.9 kg/m2, n=8) and obese (BMI>=30 kg/m2, n=7) patients undergoing radical cystectomy for MIBC. To isolate adipose stromal cells (ASCs), bladder and subcutaneous fat was digested and the stromal vascular fraction was placed into culture-specific media. The adherent ASCs were expanded, plated in 0.5% serum media and the conditioned (CM) was harvested. In addition, whole fat explants were incubated in serum-free media to harvest as whole fat CM. CM was characterized using the Millipore multi-analyte profiling. We evaluated the effect of ASC CM and whole fat CM on T24 cells migration, proliferation, and invasion. RESULTS We found several secreted factors in fat CM including Interleukin-8 and Growth Regulated Oncogene-alpha (GRO-alpha), which were highly elevated across all subjects, irrespective of BMI and fat source. Depot-specific whole fat CM from all the tested subjects increased T24 cell migration, but did not affect T24 cell proliferation or invasion. Treatment of T24 cells with GRO-alpha enhanced their migration and neutralizing antibody against GRO-alpha significantly inhibited migration. Secreted factors in the ASC CM were sufficient to induce T24 cells migration. ASC CM from an obese subject's subcutaneous fat significantly elevated T24 cell migration compared to ASC CM from normal and overweight subject's subcutaneous fat. Notably, we detected high levels of Plasminogen Inhibitor Activator-1 in ASC CM from multiple depots. Ongoing studies are focused on understanding the mechanism by which these factors promote bladder cancer progression in vivo. CONCLUSIONS Secreted factors from adipose cells collected from bladder cancer patient influence bladder tumor cells in vitro. These studies provide the first step in identifying adipose tissue-derived factors that promote bladder tumor progression. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e431 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nisha Hariharan More articles by this author Teresa Johnson-Pais More articles by this author Robert Svatek More articles by this author Keith Ashcraft More articles by this author Robin Leach More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...