Activation of AXL and antitumor effects of a monoclonal antibody to AXL in lung adenocarcinoma.
Activation of AXL and antitumor effects of a monoclonal antibody to AXL in lung adenocarcinoma.
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发表时间：
2014-04
影响因子：
2
通讯作者：
S. Iida;Y. Miki;Takashi Suzuki;K. Mori;M. Saito;H. Niikawa;T. Kondo;H. Yamada‐Okabe;H. Sasano
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作者：
S. Iida;Y. Miki;Takashi Suzuki;K. Mori;M. Saito;H. Niikawa;T. Kondo;H. Yamada‐Okabe;H. Sasano
背景/目的 AXL（anexelekto）已被探索作为非小细胞肺癌（NSCLC）的潜在新型治疗靶点，但其在 NSCLC 中的激活状态尚未得到评估。患者和方法我们首先在 112 例肺腺癌病例中免疫定位 AXL 的磷酸化形式，随后评估单克隆抗体 AXL 在两种肺腺癌细胞系 PC9 和 A549 中的抗肿瘤作用。结果 在 59.8% 的腺癌病例中检测到 Phospho-AXL 免疫反应性，并且与较大的肿瘤大小 (p=0.08) 和患者的总生存率 (p=0.041) 显着相关。体外分析结果显示，AXL 单克隆抗体显着抑制肺腺癌细胞系 PC9 和 A549 的细胞增殖，这是由抑制细胞外信号调节激酶 (ERK) 激活引起的。结论 AXL 靶向治疗可能通过抑制癌细胞的 ERK 激活，可以为肺腺癌患者带来临床益处。
BACKGROUND/AIM AXL (anexelekto) has been explored as a potential novel therapeutic target for non-small cell lung carcinoma (NSCLC) but its activation status has not been evaluated in NSCLC. PATIENTS AND METHODS We first immunolocalized the phosphorylated form of AXL in 112 lung adenocarcinoma cases and subsequently evaluated the anti-neoplastic effects of monoclonal antibody AXL in two lung adenocarcinoma cell lines, PC9 and A549. RESULTS Phospho-AXL immunoreactivity was detected in 59.8% of adenocarcinoma cases examined and tended correlate significantly with larger tumor size (p=0.08) and with overall survival of the patients (p=0.041). Results of in vitro analysis revealed that the monoclonal antibody to AXL significantly inhibited cell proliferation of PC9 and A549, lung adenocarcinoma cell lines, which was caused by an inhibition of extracellular signal-regulated kinase (ERK) activation. CONCLUSION AXL-targeted therapy, possibly through inhibiting ERK activation of carcinoma cells, could confer clinical benefits on patients with lung adenocarcinoma.