How Does Prostate Cancer Metastasize? Studying the Role of Secreted Packages (Exosomes) From Fat Tissue in Lean and Obese Patients

Study Overview
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Brief Summary
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The investigators will be collecting prostate and fat tissue from participants undergoing radical prostatectomy to culture and study in the laboratory.

Detailed Description
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Both obesity and prostate cancer are major health problems in the UK, affecting 1 in 3 and 1 in 8 men respectively. Moreover, obesity increases the risk of developing aggressive disease and the risk of prostate cancer spreading. How this happens is not known. The investigators want to understand how fat cells communicate with prostate cancer cells. Investigators will be collecting prostate and fat tissue from radical prostatectomy participants for culture, in particular to look at exosome communication.

Official Title
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The EXOPRO Study: How Does Prostate Cancer Metastasize? Understanding the Role of Exosomal Communication in Lean vs Obese Patients

Conditions
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Prostate Cancer, Obesity

Intervention / Treatment
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* Procedure: Robotic Radical Prostatectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All men undergoing radical prostatectomy at Charing Cross Hospital Exclusion Criteria: Patients unable to consent
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Obese patients<br>BMI > 25 | Procedure: Robotic Radical Prostatectomy<br>* Routine NHS Radical Prostatectomy<br>|
| Lean patients<br>BMI < or = 25 | Procedure: Robotic Radical Prostatectomy<br>* Routine NHS Radical Prostatectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine functional differences of peri-prostatic adipose tissue from lean vs obese patients on prostate cancer cell lines | Proliferation, migration, invasion, apoptosis and epthelial-mesenchymal transition assays will be performed using isolated exosomes on prostate cancer cell lines | Through to study completion, on average 3 years | 
| Identification of exosomal small RNAs transferred between human adipose tissue to prostate cancer cells lines | Exosomal RNA transferred from human adipose tissue to prostate cancer cell lines will be isolated using a tagged magnetic bead isolation method and sequenced to identify transferred small RNAs | Through to study completion, on average 3 years | 
| Assess how exosomal small RNAs from lean vs obese patients affect cancer regulation | Prostate cancer cell lines will be treated with isolated exosomes, then parental and treated cells sequenced to identify differentially expressed RNA and underlying changes | Through to study completion, on average 3 years | 
| Attempt to replicate functional changes observed | Treatment of prostate cancer cell lines with microRNA mimics or inhibitors and comparison of changes with exosome treated cell lines | Through to study completion, on average 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, Obesity, Exosomes