Pilgaard Linda, Mortensen Joachim Høg, Henriksen Michael, Olesen Pia, Sørensen Preben, Laursen Rene, Vyberg Mogens, Agger Ralf, Zachar Vladimir, Moos Torben, Duroux Meg
Laboratory of Cancer Biology, Biomedicine Group, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
Brain Pathol. 2014 Jul;24(4):360-70. doi: 10.1111/bpa.12131. Epub 2014 Mar 28.
Human glioblastoma multiforme (GBM) is an aggressive cancer with a very poor prognosis. Cripto-1 (CR-1) has a key regulatory role in embryogenesis, while in adult tissue re-expression of CR-1 has been correlated to malignant progression in solid cancers of non-neuronal origin. As CR-1 expression has yet to be described in cerebral cancer and CR-1 is regulated by signaling pathways dysregulated in GBM, we aimed to investigate CR-1 in the context of expression in GBM. The study was performed using enzyme-linked immunosorbent assay (ELISA), Western blotting, polymerase chain reaction (PCR) and immunohistochemistry to analyze the blood and tissue from 28 GBM and 4 low-grade glioma patients. Within the patient cohort, we found high CR-1 protein levels in blood plasma to significantly correlate with a shorter overall survival. We identified CR-1 in different areas of GBM tissue, including perivascular tumor cells, and in endothelial cells. Collectively, our data suggest that CR-1 could be a prognostic biomarker for GBM with the potential of being a therapeutic target.
多形性胶质母细胞瘤(GBM)是一种侵袭性癌症,预后极差。Cripto-1(CR-1)在胚胎发育中起关键调节作用,而在成体组织中,CR-1的重新表达与非神经源性实体癌的恶性进展相关。由于CR-1在脑癌中的表达尚未见报道,且CR-1受GBM中失调的信号通路调控,我们旨在研究GBM中CR-1的表达情况。该研究采用酶联免疫吸附测定(ELISA)、蛋白质印迹法、聚合酶链反应(PCR)和免疫组织化学方法,对28例GBM患者和4例低级别胶质瘤患者的血液和组织进行分析。在患者队列中,我们发现血浆中CR-1蛋白水平高与总生存期较短显著相关。我们在GBM组织的不同区域,包括血管周围肿瘤细胞和内皮细胞中鉴定出了CR-1。总体而言,我们的数据表明,CR-1可能是GBM的一种预后生物标志物,具有成为治疗靶点的潜力。