Montreal Children's Hospital, McGill University, Montreal, QC.
Blood. 2010 Aug 5;116(5):815-8. doi: 10.1182/blood-2009-10-250639. Epub 2010 May 12.
Cancer cells frequently overexpress tissue factor (TF) and become procoagulant. This conversion may be driven by genetic transformation, including through the expression of the oncogenic epidermal growth factor receptor (EGFR) and its mutant, EGFRvIII, present in glioblastoma multiforme (GBM). Here we show that the EGFRvIII-dependent GBM cell transformation is associated with the onset of the simultaneous overexpression of TF, protease-activated receptors 1 and 2 (PAR1 and PAR2), and ectopic synthesis of factor VII (FVII). Efficient generation of factor Xa by these cells still requires exogenous FVIIa. However, as a result of EGFRvIII-dependent transformation, GBM cells become hypersensitive to TF/PAR-mediated signaling and produce ample angiogenic factors (vascular endothelial growth factor and interleukin-8) on exposure to FVIIa and PAR1- or PAR2-activating peptides. Thus, oncogenes may cause complex changes in the ability of GBM cancer cells to interact with the coagulation system, thereby exacerbating its influence on angiogenesis and disease progression.
癌细胞经常过度表达组织因子 (TF) 并变得促凝。这种转化可能是由遗传转化驱动的，包括通过表达存在于多形性胶质母细胞瘤 (GBM) 中的致癌表皮生长因子受体 (EGFR) 和其突变体 EGFRvIII。在这里，我们表明 EGFRvIII 依赖性 GBM 细胞转化与 TF、蛋白酶激活受体 1 和 2 (PAR1 和 PAR2) 的同时过度表达以及因子 VII (FVII) 的异位合成的开始相关。这些细胞中有效产生因子 Xa 仍需要外源性 FVIIa。然而，由于 EGFRvIII 依赖性转化，GBM 细胞对 TF/PAR 介导的信号转导变得敏感，并在暴露于 FVIIa 和 PAR1 或 PAR2 激活肽时产生大量血管生成因子（血管内皮生长因子和白细胞介素-8）。因此，癌基因可能导致 GBM 癌细胞与凝血系统相互作用的能力发生复杂变化，从而加剧其对血管生成和疾病进展的影响。
