Marthick James R, Dickinson Joanne L
Menzies Research Institute Tasmania, University of Tasmania, 17 Liverpool Street Hobart, TAS 7000, Australia.
Prostate Cancer. 2012;2012:298732. doi: 10.1155/2012/298732. Epub 2012 Jul 31.
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 α(2) and integrin α(6) 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 α(2) and α(6) integrins in clinical applications for tailored patient treatment.
前列腺癌的遗传结构复杂，受多基因影响，尽管最近取得了重大进展，但仍有许多问题存在。基因技术的进步极大地提高了我们识别与包括前列腺癌在内的复杂疾病相关的基因变异的能力。全基因组关联研究（GWAS）和微阵列基因表达研究已经确定了与前列腺癌易感性和肿瘤发展相关的基因关联。整合素在研究前列腺肿瘤发展的潜在遗传易感性和机制的两项研究中都占据显著地位。整合素是参与细胞外和细胞内信号传导的细胞粘附分子，对肿瘤发展、迁移和血管生成至关重要。虽然几种整合素与肿瘤发展有关，但整合素α(2)和整合素α(6)的作用是本文的重点，因为现在有证据表明这些整合素与前列腺癌易感性、癌症干细胞生物学、血管生成、细胞迁移以及骨转移有关，并且代表了潜在的生物标志物和治疗靶点。目前迫切需要开发能够区分惰性前列腺癌和侵袭性前列腺癌并预测患者对治疗反应的工具。本文概述了支持将α(2)和α(6)整合素用于临床以实现个性化患者治疗的证据。
