• Po-Len Liu, Jong-Rung Tsai, Jhi-Jhu Hwang, Shah-Hwa Chou, Yu-Jen Cheng, Feng-Yen Lin, Yuh-Lien Chen, Chun-Ying Hung, Wen-Chi Chen, Yung-Hsiang Chen, and Inn-Wen Chong.
• Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.
• Am. J. Respir. Cell Mol. Biol. 2010 Nov 1; 43 (5): 530-8.

AbstractHigh-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.

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