Overall VF mucosal function as well as the importance of investigating complete functional protein-glycan groups using system

Our IHC analysis on bladder cancer TMAs showed that ETK expression is increased in bladder cancer tissues compared with their benign counterparts. Considering that targeted expression of ETK in mouse prostate leads to the development of PIN, it is possible that ETK may also play a role in oncogenic transformation in bladder urothelial cells. More importantly, ETK expression is higher in invasive than non-invasive bladder tumors, suggesting that ETK may also play a role in tumor invasion and metastasis. This possibility was supported by our observation that knockdown of ETK expression in bladder cancer cells inhibit their activity in in vitro invasion assays. Furthermore, we found that ETK expression level also can predict survival of patients with cystectomy treatment independent of other important clinicopathological variables including age, tumor grade, stage and positive lymph node status. Therefore, ETK may potentially serve as a new drug target for bladder cancer treatment as well as a biomarker which could be used to stratify patients with higher mortality risk. These patients may be beneficial from therapeutics targeting ETK activity. The vocal fold mucosa is a complex multi-layered biological system consisting of a squamous cell epithelium, basement membrane and lamina propria. Each mucosal layer holds a distinct set of functions that are together responsible for VF immune, transport and barrier capabilities, the ability to absorb considerable impact stress, and favorable viscoelasticity for self-sustained tissue oscillation and voice production. The epithelium and basement membrane represent the most superficial layers of the VF mucosa and jointly provide a protective physical barrier against mucosal insult. Surface epithelial cells signal professional immune cells in response to incident challenges from the upper airway and mediate water and ion transport for the maintenance of VF surface hydration. Deep to the basement membrane, the LP is populated by sparsely distributed fibroblast cells housed in a biomechanically favorable extracellular matrix. ECM fibrous proteins confer three-dimensional matrix organization, strength and elasticity ; whereas interstitial glycans influence matrix viscosity, hydration and volume. These proteins and glycans are functionally interdependent within the ECM, and often operate in a synchronous and coordinated fashion. For example, decorin modulates stress transmission along collagen fibrils, and also influences fibril organization; fibromodulin binds to collagen and regulates collagen synthesis; fibronectin facilitates cell adhesion and upregulates collagen at wound sites; and DAPT versican binds to hyaluronic acid, allows compression, and dissipates impact stress. These coordinated interactions underscore the inherent complexity of both ECM.

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