Abstract
BackgroundProstate cancer is the second most frequently diagnosed cancer in men worldwide. Current treatments include surgery, androgen ablation and radiation. Introduction of more targeted therapies in prostate cancer, based on a detailed knowledge of the signalling pathways, aims to reduce side effects, leading to better clinical outcomes for the patient. ADAM19 (A Disintegrin And Metalloproteinase 19) is a transmembrane and soluble protein which can regulate cell phenotype through cell adhesion and proteolysis. ADAM19 has been positively associated with numerous diseases, but has not been shown to be a tumor suppressor in the pathogenesis of any human cancers. Our group sought to investigate the role of ADAM19 in human prostate cancer.MethodsADAM19 mRNA and protein levels were assessed in well characterised human prostate cancer cohorts. ADAM19 expression was assessed in normal prostate epithelial cells (RWPE-1) and prostate cancer cells (LNCaP, PC3) using western blotting and immunocytochemistry. Proliferation assays were conducted in LNCaP cells in which ADAM19 was over-expressed. In vitro scratch assays were performed in PC3 cells over-expressing ADAM19.ResultsImmunohistochemical studies highlighted that ADAM19 protein levels were elevated in normal prostate tissue compared to prostate cancer biopsies. Results from the clinical cohorts demonstrated that high levels of ADAM19 in microarrays are positively associated with lower stage (p = 0.02591) and reduced relapse (p = 0.00277) of human prostate cancer. In vitro, ADAM19 expression was higher in RWPE-1 cells compared to LNCaP cells. In addition, human ADAM19 over-expression reduced LNCaP cell proliferation and PC3 cell migration.ConclusionsTaken together, our immunohistochemical and microarray results and cellular studies have shown for the first time that ADAM19 is a protective factor for human prostate cancer. Further, this study suggests that upregulation of ADAM19 expression could be of therapeutic potential in human prostate cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2178-4) contains supplementary material, which is available to authorized users.
Highlights
Prostate cancer is the second most frequently diagnosed cancer in men worldwide
High ADAM19 expression correlates with increased disease-free survival from prostate cancer, and lower tumour stage In order to evaluate the relationship between ADAM19 levels and prostate cancer, we studied ADAM19 expression in publicly available microarray data from two distinct cohorts of prostate cancer patients
Our study provides evidence that elevated ADAM19 expression may serve as a tumor suppressor in human prostate cancer
Summary
Prostate cancer is the second most frequently diagnosed cancer in men worldwide. Introduction of more targeted therapies in prostate cancer, based on a detailed knowledge of the signalling pathways, aims to reduce side effects, leading to better clinical outcomes for the patient. Early-stage prostate cancer tumours require androgens as growth factors for proliferation and survival [2]. Androgen ablation therapy impacts the growth and survival of normal prostate epithelium [2] and has an undesirable effect on body composition and other physiological and metabolic parameters, increasing the risks for other diseases, such as osteoporosis [4]. Increased specificity of treatment reduces the risk of these side effects and is more likely to result in long term decreases in proliferation and metastasis of cancer, leading to improved clinical outcomes [5]. It is important to further develop treatment options which target prostate cancer cells [5]
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