Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
Biochem Biophys Res Commun. 2012 Apr 27;421(1):140-4. doi: 10.1016/j.bbrc.2012.03.144. Epub 2012 Apr 4.
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.
间皮瘤是一种高度恶性肿瘤,预后不良,治疗选择有限。顺铂(CDDP)虽然是一种有效的抗癌药物,但它的响应率仅为 20%。因此,发现生物标志物以区分顺铂敏感与耐药病例是可取的。为此,进行了差异蛋白质组分析以区分不同顺铂敏感性的间皮瘤细胞,结果显示 Annexin A4(ANXA4)蛋白在耐药细胞中的表达高于敏感细胞。此外,人临床恶性间皮瘤组织中的 ANXA4 表达水平高于良性间皮瘤和正常间皮组织。最后,在间皮瘤细胞中敲低 ANXA4 基因后观察到易感性增加,而转染 ANXA4 质粒后则观察到相反的效果。这些结果表明,ANXA4 具有与间皮瘤细胞顺铂敏感性相关的调节功能,并且它可能是病理诊断中顺铂敏感性的生物标志物。