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Emerging Putative Biomarkers: The Role of Alpha 2 and 6 Integrins in Susceptibility, Treatment, and Prognosis

DOI: 10.1155/2012/298732

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Abstract:

The genetic architecture underpinning prostate cancer is complex, polygenic and despite recent significant advances many questions remain. Advances in genetic technologies have greatly improved our ability to identify genetic variants associated with complex disease including prostate cancer. Genome-wide association studies (GWASs) and microarray gene expression studies have identified genetic associations with prostate cancer susceptibility and tumour development. The integrins feature prominently in both studies examining the underlying genetic susceptibility and mechanisms driving prostate tumour development. Integrins are cell adhesion molecules involved in extracellular and intracellular signalling and are imperative for tumour development, migration, and angiogenesis. Although several integrins have been implicated in tumour development, the roles of integrin and integrin are the focus of this paper as evidence is now emerging that these integrins are implicit in prostate cancer susceptibility, cancer stem cell biology, angiogenesis, cell migration, and metastases to bone and represent potential biomarkers and therapeutic targets. There currently exists an urgent need to develop tools that differentiate indolent from aggressive prostate cancers and predict how patients will respond to treatment. This paper outlines the evidence supporting the use of and integrins in clinical applications for tailored patient treatment. 1. Introduction The diagnosis of aggressive prostate cancer at an early stage is crucial for successful management; however, clinicians still lack the diagnostic tools to identify indolent tumours from those likely to be aggressive and with a propensity to metastasise. Currently, the prostate-specific antigen (PSA) test still remains a widely used marker of choice for diagnosis and monitoring the progression of prostate cancer [1]. Thus molecular markers that can characterise individuals with a genetic susceptibility to prostate cancer identify malignant potential, provide real-time tumour surveillance, and potentially offer therapeutic intervention represent a major focus of current research. The advent of high-throughput genetic mapping technologies has not only highlighted the heterogeneity and complexity of the disease but also identified key molecules driving prostate cancer development and progression, and these molecules include the integrins. The integrins represent a large family of cell surface receptors that are responsible for cellular adhesion and complex formation with ligands within the extracellular matrix (ECM).

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