Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.
Am J Respir Cell Mol Biol. 2010 Nov;43(5):530-8. doi: 10.1165/rcmb.2009-0269OC. Epub 2009 Nov 20.
High-mobility group box 1 (HMGB1) is a versatile protein with intranuclear and extracellular functions. It is involved in invasion and metastasis in various human malignancies. However, the role of HMGB1 in non-small cell lung cancer (NSCLC) is unclear. We hypothesized that HMGB1 expression is a determinant of cellular invasiveness and metastasis in lung cancer. We examined HMGB1 expression in 48 NSCLC specimens by quantitative real-time PCR. High HMGB1 expression was significantly associated with clinically advanced stages (stage III-IV) (P < 0.05) and was correlated to expression of matrix metalloproteinase-9 (MMP-9) (P < 0.05). Patients with high levels of HMGB1 expression had poorer clinical prognosis. The expression level of MMP-9 and metastatic ability in vitro were significantly higher in an HMGB1-overexpressing human NSCLC cell lines (A549 and H23). The treatment with HMGB1 small interfering RNA reduced MMP-9 expression and the cellular metastatic ability in NSCLC cells. We also demonstrated that phosphoinositide 3-kinase/Akt and NF-κB-related pathways contributed to the HMGB1-induced MMP-9 expression and cellular metastatic ability.
高迁移率族蛋白 B1（HMGB1）是一种具有核内和细胞外功能的多功能蛋白。它参与各种人类恶性肿瘤的侵袭和转移。然而，HMGB1 在非小细胞肺癌（NSCLC）中的作用尚不清楚。我们假设 HMGB1 表达是肺癌细胞侵袭和转移的决定因素。我们通过实时定量 PCR 检测了 48 例 NSCLC 标本中 HMGB1 的表达。高 HMGB1 表达与临床晚期（III-IV 期）显著相关（P < 0.05），并与基质金属蛋白酶-9（MMP-9）的表达相关（P < 0.05）。HMGB1 高表达的患者临床预后较差。HMGB1 过表达的人 NSCLC 细胞系（A549 和 H23）中 MMP-9 的表达水平和体外转移能力显著升高。用 HMGB1 小干扰 RNA 处理可降低 NSCLC 细胞中 MMP-9 的表达和细胞转移能力。我们还表明，磷酸肌醇 3-激酶/Akt 和 NF-κB 相关途径有助于 HMGB1 诱导的 MMP-9 表达和细胞转移能力。
