Dr. Yves Fradet
Laval University – Quebec City
 
In vitro model of human primary prostate cells for the assessment of anti-inflammatory properties of chemopreventive agents
 
Basic/Translational - Diagnostic
 
Inflammation is a natural process through which injured cells within tissues secrete products that attract cells of the immune system to defend themselves against infections or to repair injuries. However, this phenomenon may occur in a chronic manner in various organs, in response to diverse insults such as repeated infections, trauma, or hormonal and dietary factors. Such chronic inflammation has been linked to the development of approximately 20% of all human cancers. Recent evidence suggests that this process plays a role in the development of prostate cancer. The risk of suffering from prostate cancer varies between countries, being low for example in Southeast Asia and higher in Western countries. However, when Chinese or Japanese men immigrate to Western countries, their risk of prostate cancer rapidly increases. These observations underline the importance of environmental factors such as the diet, in defining the risk of prostate cancer.
 
Dr. Fradet’s team developed a model based on growing prostate cells in the laboratory, to help adapt preventive interventions to individual men, and provide a tool to evaluate the interventions’ impact on prostate inflammation. The evaluation of patients at risk for prostate cancer includes taking prostate biopsy samples. For biopsied patients for whom no cancer is detected or only low risk cancer at first biopsy an adapted diet, aimed at reducing prostate inflammation, might prevent development or progression of the disease. Cells from the prostate of more than 20 patients who had prostatectomy were grown in culture. The cells were successfully frozen and remained in good condition after thawing for use in experiments. At least 5 vials of prostate cells for each patient were frozen. The  optimal conditions were determined for measuring the secretion in the cell medium of molecules involved in promoting inflammation, thus evaluating the intrinsic inflammation of cells. A higher level of intrinsic inflammation was observed in the presence of more aggressive cancers. Conditions were optimized for inducing an artificial state of inflammation using a product that mimics a viral infection. The effect of 4 micronutrients were tested with anti-inflammatory properties: gingerol, capsaicin, resveratrol and omega-3 fat (fish oil from menhaden) on the primary prostatic epithelial cell cultures. For this purpose, the cell cultures were either pre-treated or not treated with the micronutrients, 20 hours before induction of inflammation. It was observed that some micronutrients could decrease the induced inflammation but that the response varied between patients. These results indicate that the anti-inflammatory potential of the micronutrients seems to be specific to individual primary prostatic epithelial cell cultures and support the hypothesis that these cultures could be used to adapt preventive recommendations for individual patients. It was also observed that fish oil is the most efficient anti-inflammatory micronutrient.
 
A model is now available to characterize the intrinsic inflammation present in the prostate with a potential method to reduce the inflammation.

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