Dataset Information

Adipose Tissue-Secreted Factors Alter Bladder Cancer Cell Migration.

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.

SUBMITTER: Hariharan N

PROVIDER: S-EPMC5985104 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Adipose Tissue-Secreted Factors Alter Bladder Cancer Cell Migration.

Hariharan Nisha N Ashcraft Keith A KA Svatek Robert S RS Livi Carolina B CB Wilson Desiree D Kaushik Dharam D Leach Robin J RJ Johnson-Pais Teresa L TL

Journal of obesity 20180520

<h4>Background</h4>Obesity is associated with an increased risk of bladder cancer recurrence. This study investigated the role of adipose tissue in bladder cancer progression.<h4>Methods</h4>Gene expression profiling was performed on adipose tissues collected from normal weight (<i>n</i>=5), overweight (<i>n</i>=11), and obese (<i>n</i>=10) patients with invasive bladder cancer, and adipose stromal cells (ASCs) were obtained from two normal weight, two overweight, and two obese patients. Conditi ...[more]

PMID: 29887999

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Project description:Inadequate or inappropriate implantation and placentation during the establishment of human pregnancy is thought to lead to first trimester miscarriage, placental insufficiency and other obstetric complications. To create the placental blood supply, specialized cells, the 'extravillous trophoblast' (EVT) invade through the differentiated uterine endometrium (the decidua) to engraft and remodel uterine spiral arteries. We hypothesized that decidual factors would regulate EVT function by altering the production of EVT membrane and secreted factors. We used a proteomics approach to identify EVT membrane and secreted proteins regulated by decidual cell factors. Human endometrial stromal cells were decidualized in vitro by treatment with estradiol (10(-8) M), medroxyprogesterone acetate (10(-7) M) and cAMP (0.5 mM) for 14 days. Conditioned media (CM) was collected on day 2 (non-decidualized CM) and 14 (decidualized CM) of treatment. Isolated primary EVT cultured on Matrigel™ were treated with media control, non-decidualized or decidualized CM for 16 h. EVT CM was fractionated for proteins <30 kDa using size-exclusion affinity nanoparticles (SEAN) before trypsin digestion and HPLC-MS/MS. 43 proteins produced by EVT were identified; 14 not previously known to be expressed in the placenta and 12 which had previously been associated with diseases of pregnancy including preeclampsia. Profilin 1, lysosome associated membrane glycoprotein 1 (LAMP1), dipeptidyl peptidase 1 (DPP1/cathepsin C) and annexin A2 expression by interstitial EVT in vivo was validated by immunhistochemistry. Decidual CM regulation in vitro was validated by western blotting: decidualized CM upregulated profilin 1 in EVT CM and non-decidualized CM upregulated annexin A2 in EVT CM and pro-DPP1 in EVT cell lysate. Here, non-decidualized factors induced protease expression by EVT suggesting that non-decidualized factors may induce a pro-inflammatory cascade. Preeclampsia is a pro-inflammatory condition. Overall, we have demonstrated the potential of a proteomics approach to identify novel proteins expressed by EVT and to uncover the mechanisms leading to disease states.

Dataset Information

Adipose Tissue-Secreted Factors Alter Bladder Cancer Cell Migration.

Publications

Adipose Tissue-Secreted Factors Alter Bladder Cancer Cell Migration.

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