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Senescence-Induced Alterations in the Laminin Component of Prostate Epithelial Extracellular Matrix Regulate Progression of Prostate Cancer

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Final rept. 16 Dec 2006-15 Dec 2008

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The purpose of this work was to determine how changes in laminin chains associated with senescence affected prostate cancer progression. In order to determine the effects of alterations to the laminin component of the tumor microenvironment, I overexpressed the laminin alpha 4, beta 2, or alpha 4 and beta 2 chains in a human prostate cancer cell line. I demonstrated that these lines secreted the specific laminin chains and incorporated them into the extracellular matrix. Stable expression of the laminin alpha 4 chain resulted in increased in vitro migration and increased in vivo angiogenesis and tumorigenicity of those cells compared to empty vector control cells. High expression of both the laminin alpha 4 and beta 2 chains decreased in vitro proliferation and migration and decreased in vivo tumorigenicity compared to control cells. Stable expression of the laminin beta 2 chain alone had a tumor promoting function as opposed to the tumor suppressive role seen with high protein levels of the laminin alpha 4 and beta 2 chains together. These data support the concept that since senescent cells secrete both tumor promoting and tumor inhibiting factors, it is the interaction of these factors that infl ences cellular behavior This dichotom also points to the importance of nderstanding

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  • Anatomy and Physiology
  • Medicine and Medical Research

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