Annexin A4 is a possible biomarker for cisplatin susceptibility of malignant mesothelioma cells
Annexin A4 is a possible biomarker for cisplatin susceptibility of malignant mesothelioma cells
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DOI：
10.1016/j.bbrc.2012.03.144
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发表时间：
2012-04-27
影响因子：
3.1
通讯作者：
Tsunoda, Shin-ichi
中科院分区：
文献类型：
--
作者：
Yamashita, Takuya;Nagano, Kazuya;Tsunoda, Shin-ichi
间皮瘤是一种高度恶性肿瘤，预后差，治疗选择有限。顺铂（cisplatin，CDDP）是一种有效的抗肿瘤药物，但其有效率仅为20%.因此，需要发现生物标志物来区分CDDP敏感与耐药病例。为此，进行差异蛋白质组分析以区分不同CDDP敏感性的间皮瘤细胞，这揭示了CDDP抗性细胞中膜联蛋白A4（ANXA 4）蛋白的表达高于CDDP敏感性细胞。此外，ANXA 4在人类临床恶性间皮瘤组织中的表达水平高于良性间皮瘤和正常间皮瘤组织。最后，在间皮瘤细胞中ANXA 4基因敲低后观察到易感性增加，而ANXA 4质粒转染后观察到相反的效果。这些结果表明，ANXA 4具有与间皮瘤细胞的顺铂敏感性相关的调节功能，并且其可以在病理诊断中作为CDDP敏感性的生物标志物。(C)2012 Elsevier Inc. All rights reserved.
Mesothelioma is a highly malignant tumor with a poor prognosis and limited treatment options. Although cisplatin (CDDP) is an effective anticancer drug, its response rate is only 20%. Therefore, discovery of biomarkers is desirable to distinguish the CDDP-susceptible versus resistant cases. To this end, differential proteome analysis was performed to distinguish between mesothelioma cells of different CDDP susceptibilities, and this revealed that expression of annexin A4 (ANXA4) protein was higher in CDDP-resistant cells than in CDDP-susceptible cells. Furthermore, ANXA4 expression levels were higher in human clinical malignant mesothelioma tissues than in benign mesothelioma and normal mesothelial tissues. Finally, increased susceptibility was observed following gene knockdown of ANXA4 in mesothelioma cells, whereas the opposite effect was observed following transfection of an ANXA4 plasmid. These results suggest that ANXA4 has a regulatory function related to the cisplatin susceptibility of mesothelioma cells and that it could be a biomarker for CDDP susceptibility in pathological diagnoses. (C) 2012 Elsevier Inc. All rights reserved.