Tait Catherine R, Jones Pamela F
Molecular Medicine Unit, University of Leeds, Clinical Sciences Building, St James's University Hospital, Leeds L9 7TF, UK.
J Pathol. 2004 Sep;204(1):1-10. doi: 10.1002/path.1618.
On first view, the literature pertaining to the expression of the angiopoietins in tumours is confusing and does not readily offer a consensus pattern. Apparently conflicting publications report increased, decreased or unchanged expression levels of both angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) in a wide range of tumours. However, closer scrutiny of the literature, taking into account relative increases or decreases of each factor, reveals a consensus pattern, seen in almost all instances of expression profiling of the angiopoietins in tumours. What becomes apparent is that although absolute levels of either angiopoietin may increase or decrease, the ratio of Ang-1:Ang-2 shifts in favour of Ang-2. Given that Ang-2 is a destabilization factor, rendering vasculature in a more plastic state amenable to sprouting (under the influence of vascular endothelial growth factor, VEGF) or regression, this analysis suggests that tumours shift the angiogenic balance towards a pro-angiogenic state through altering the balance between the angiopoietins. This in turn implicates Ang-2 as a candidate for the angiogenic switch and also as an important potential therapeutic target.
乍一看,有关血管生成素在肿瘤中表达的文献令人困惑,且难以形成一致的模式。显然,相互矛盾的出版物报道了血管生成素-1(Ang-1)和血管生成素-2(Ang-2)在多种肿瘤中的表达水平升高、降低或无变化。然而,仔细审视这些文献,考虑到每种因子的相对增减情况,会发现一种一致的模式,几乎在所有肿瘤血管生成素表达谱分析的实例中都能看到。显而易见的是,尽管任一血管生成素的绝对水平可能升高或降低,但Ang-1:Ang-2的比值会向有利于Ang-2的方向转变。鉴于Ang-2是一种去稳定因子,可使血管处于更易发生出芽(在血管内皮生长因子,即VEGF的影响下)或退化的可塑性状态,该分析表明肿瘤通过改变血管生成素之间的平衡,将血管生成平衡转向促血管生成状态。这反过来意味着Ang-2是血管生成开关的候选因子,也是一个重要的潜在治疗靶点。