黏着斑激酶-原癌基因酪氨酸蛋白激酶-桩蛋白系统在人类神经母细胞瘤中的表达及疾病转归
FAK-Src-paxillin system expression and disease outcome in human neuroblastoma.
作者信息
Kratimenos Panagiotis, Koutroulis Ioannis, Syriopoulou Vasiliki, Michailidi Christina, Delivoria-Papadopoulos Maria, Klijanienko Jerzy, Theocharis Stamatios
机构信息
a Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Children's National Medical Center , The George Washington University, School of Medicine and Health Sciences , Washington, DC , USA.
b First Department of Pathology , National and Kapodistrian University of Athens, School of Medicine , Athens , Greece.
出版信息
Pediatr Hematol Oncol. 2017 May;34(4):221-230. doi: 10.1080/08880018.2017.1360969. Epub 2017 Oct 17.
BACKGROUND
Neuroblastoma (NB) often presents with metastatic disease and poor survival. The need for new prognostic markers remains invaluable. The FAK-Src-Paxillin protein system is associated with aggressive phenotype in adult malignancies but is largely unexplored in pediatric NB.
OBJECTIVE
To assess FAK-Src-Paxillin protein expression in human NB cell lines and clinical cytology material and to delineate its association with survival.
DESIGN/METHODS: Western blot and immunohistochemistry were applied for FAK-Src-Paxillin expression in NB cell lines and 23 human cytology specimens, respectively. Protein expression in human clinical samples was correlated with clinicopathological parameters, MYCN amplification and survival.
RESULTS
FAK, Src and Paxillin proteins are expressed in human NB cells lines, and can be detected in clinical cytology specimens from NB patients, (59%, 32% and 33% respectively). Simultaneous FAK-Src-Paxillin expression was noted in 30% of NB patients. Children with concomitant positivity FAK, Src, and Paxillin tumors, as well as MYCN amplification, had increased mortality compared to those without.
CONCLUSIONS
FAK-Src-Paxillin system is a marker of unfavorable prognosis for human NB patients but also a promising therapeutic target.
背景
神经母细胞瘤（NB）常伴有转移性疾病且生存率低。对新的预后标志物的需求仍然非常重要。黏着斑激酶（FAK）-Src-桩蛋白（Paxillin）蛋白系统与成人恶性肿瘤的侵袭性表型相关，但在儿童NB中基本未被探索。
目的
评估FAK-Src-Paxillin蛋白在人NB细胞系和临床细胞学材料中的表达，并阐明其与生存率的关系。
设计/方法：分别采用蛋白质印迹法和免疫组织化学法检测NB细胞系和23例人类细胞学标本中FAK-Src-Paxillin的表达。将人类临床样本中的蛋白表达与临床病理参数、MYCN扩增及生存率进行关联分析。
结果
FAK、Src和Paxillin蛋白在人NB细胞系中表达，并可在NB患者的临床细胞学标本中检测到（分别为59%、32%和33%）。30%的NB患者同时表达FAK-Src-Paxillin。与无FAK、Src和Paxillin肿瘤同时阳性以及MYCN扩增的儿童相比，有这些情况的儿童死亡率更高。
结论
FAK-Src-Paxillin系统是人类NB患者预后不良的标志物，但也是一个有前景的治疗靶点。
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