MECHANOTRANSDUCTION IN THE DEVELOPING MURINE PROSTATE
Date
2019-05
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Publisher
University of Delaware
Abstract
Prostate cancer and benign prostate hyperplasia (BPH) are two of the most common diseases affecting men - with 50% of middle-aged men suffering from BPH and 12% of men diagnosed with prostate cancer in their lifetime. Both pathologies involve dysregulated epithelial growth and structural abnormalities that influence the mechanical forces experience within the prostate lumen. As the role some smooth muscle contraction and mechanically sensitive ion channels are elucidated in both the developing and adult prostate, compounding evidence suggests that changes in mechanical forces experienced by the epithelial cells both pathologically and in development could influence epithelial phenotype and abnormal growth evident in BPH and cancer. To understand the type and impact of these forces on benign and malignant growth, it is pertinent to understand the impact of mechanical forces on normal/regulated epithelial growth during development. To study this, a 3D model with high physiological relevance is needed. Therefore, the first aim of this project is to develop successful 3D culture models that allows one to alter various mechanical forces both intraluminally and externally of the prostate. The second aim entails using such a model to determine whether fluid induced forces influence prostatic cell differentiation, expression, and phenotype in respect to the general morphology in development. The results suggest that the morphology and epithelial growth rate of the prostate does change in response to intralumenal pressure and environmental density. The models and preliminary data documented in this project are a critical step towards a comprehensive understanding of the role of mechanical forces in prostate disease.
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Keywords
Neuroscience, Mechanotransduction,Murine prostate