Abstract

Background Obesity is associated with an increased risk of bladder cancer recurrence. This study investigated the role of adipose tissue in bladder cancer progression. Methods Gene expression profiling was performed on adipose tissues collected from normal weight (n=5), overweight (n=11), and obese (n=10) patients with invasive bladder cancer, and adipose stromal cells (ASCs) were obtained from two normal weight, two overweight, and two obese patients. Conditioned media (CM) was characterized and evaluated for its effects on the proliferation, migration, and invasive potential of T24 bladder cancer cells. Results Expression profiling demonstrated depot-specific or body mass index-specific differences. Increased T24 cell migration was observed using CM harvested from all ASCs. ASC CM from an obese patient significantly increased T24 cell migration and invasion compared to ASC CM collected from normal weight and overweight patients. We identified abundant expression of CXCL1, PAI1, IL6, CX3CL1, and CCL2 in all CM. Exogenous treatment of T24 cells with PAI1, IL6, and CXCL1 enhanced migration. Depletion of CXCL1, PAI1, and IL6 in an obese patient ASC CM abrogated T24 migration. Conclusion Factors secreted by adipose tissue influence the migration of bladder tumor cells and could play an active role in tumor progression.

Highlights

  • An estimated 79,000 urinary bladder cancer cases will be newly diagnosed and are expected to result in 16,870 deaths in the United States in 2017 [1]

  • An increasing number of studies point towards a positive association between body mass index (BMI) and bladder cancer risk. erefore, it is important to understand how adipose tissue exerts its effects on the bladder tumor progression

  • Is study demonstrates that visceral adipose tissue is a potential source of secreted factors that can induce bladder cancer cell migration in vitro, and the adipose stromal cells (ASCs) population is a source of factors that have the potential to impact bladder carcinogenesis

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Summary

Introduction

An estimated 79,000 urinary bladder cancer cases will be newly diagnosed and are expected to result in 16,870 deaths in the United States in 2017 [1]. An epidemiological study of 1,719 incident bladder cancer cases demonstrated that obese individuals had a 28% increased risk for bladder cancer compared to normal weight individuals [5]. In patients with body mass index (BMI) > 30 kg/m2, there was a 67% increased risk of cancer recurrence and a 43% increased risk of cancer-specific mortality [6]. Is study investigated the role of adipose tissue in bladder cancer progression. Gene expression profiling was performed on adipose tissues collected from normal weight (n 5), overweight (n 11), and obese (n 10) patients with invasive bladder cancer, and adipose stromal cells (ASCs) were obtained from two normal weight, two overweight, and two obese patients. Factors secreted by adipose tissue influence the migration of bladder tumor cells and could play an active role in tumor progression

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