Osteopontin promotes cancer cell drug resistance, invasion, and lactate production and is associated with poor outcome of patients with advanced non-small-cell lung cancer.
Osteopontin promotes cancer cell drug resistance, invasion, and lactate production and is associated with poor outcome of patients with advanced non-small-cell lung cancer.
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DOI：
10.2147/ott.s164007
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发表时间：
2018
影响因子：
4
通讯作者：
Huang J
中科院分区：
文献类型：
--
作者：
Ouyang X;Huang Y;Jin X;Zhao W;Hu T;Wu F;Huang J
骨桥蛋白 (OPN) 是小整合素结合配体 N 连接糖蛋白家族的成员，已在多种类型的人类恶性肿瘤中进行了分析。本研究检测了 OPN 的表达水平，并评估了其在非小细胞肺癌 (NSCLC) 患者肿瘤进展中的作用。使用免疫组织化学方法检测 101 个 NSCLC 肿瘤中的 OPN 表达水平。晚期NSCLC与I/II期NSCLC的mRNA和蛋白水平存在显着差异。在OPN干扰的癌细胞中检测NSCLC癌细胞系（A549和SK-MES-1）的耐药性、侵袭能力和乳酸产生。免疫染色表明OPN主要表达于NSCLC细胞的细胞质中。此外，OPN 与 NSCLC 临床特征相关。结果表明，OPN 表达水平与癌症分化、远处转移和铂类治疗的疗效显着相关。值得注意的是，结果确定 OPN 表达水平是使用多变量分析预测细胞对一线铂类化疗反应以及预测癌症分化和远处转移的潜在因素。此外，废除 OPN 水平会减少 NSCLC 细胞中乳酸的产生，并与乳酸脱氢酶 A (LDHA) 的下调同时发生。目前的研究结果表明，OPN 或许能够预测患者的不良预后和顺铂耐药。
Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy. The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC). OPN expression levels were detected using immunohistochemistry in 101 NSCLC tumors. The mRNA and protein levels have significant difference between advanced NSCLC and stage I/II NSCLC. The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN. Immunostaining indicated that OPN was primarily expressed in the cytoplasm of NSCLC cells. Moreover, OPN correlates with NSCLC clinical traits. The results demonstrated that OPN expression levels significantly correlated with cancer differentiation, distant metastasis and the efficacy of platinum-based treatment. Notably, the results identified OPN expression levels as a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis. Additionally, the abrogation of OPN levels reduced lactate production in NSCLC cells and occurred along side with the downregulation of lactate dehydrogenase A (LDHA). The results of the current study suggest that OPN may be able to predict poor prognosis and cisplatin resistance in patients.