Bing-sheng Sun1, Jian You, Yue Li, Zhen-fa Zhang, Chang-li Wang. 1. Department of Lung Cancer Surgery, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin Lung Cancer Center, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin 300060, China.
Abstract
BACKGROUND: Osteopontin (OPN) was identified as one of the leading genes that promote the metastasis of malignant tumor. However, the mechanism by which OPN mediates metastasis in non-small cell lung cancer (NSCLC) remains unknown. The aim of the study is to investigate the biological significance and the related molecular mechanism of OPN expression in lung cancer cell line. METHODS: Lentiviral-mediated RNA interference was applied to inhibit OPN expression in metastatic human NSCLC cell line (A549). The invasion, proliferation, and metastasis were evaluated OPN-silenced in A549 cells in vitro and in vivo. The related mechanism was further investigated. RESULTS: Interestingly, OPN knockdown significantly suppressed the invasiveness of A549 cells, but had only a minor effect on the cellular migration and proliferation. Moreover, we demonstrated that OPN knockdown significantly reduced the levels of matrix metalloproteinase (MMP)-2 and urokinase plasminogen activator (uPA), and led to an obvious inhibition of both in vitro invasion and in vivo lung metastasis of A549 cells (P < 0.001). CONCLUSIONS: Our data demonstrate that OPN contributes to A549 cell metastasis by stimulating cell invasion, independent of cellular migration and proliferation. OPN could be a new treatment target of NSCLC.
BACKGROUND:Osteopontin (OPN) was identified as one of the leading genes that promote the metastasis of malignant tumor. However, the mechanism by which OPN mediates metastasis in non-small cell lung cancer (NSCLC) remains unknown. The aim of the study is to investigate the biological significance and the related molecular mechanism of OPN expression in lung cancer cell line. METHODS: Lentiviral-mediated RNA interference was applied to inhibit OPN expression in metastatic humanNSCLC cell line (A549). The invasion, proliferation, and metastasis were evaluated OPN-silenced in A549 cells in vitro and in vivo. The related mechanism was further investigated. RESULTS: Interestingly, OPN knockdown significantly suppressed the invasiveness of A549 cells, but had only a minor effect on the cellular migration and proliferation. Moreover, we demonstrated that OPN knockdown significantly reduced the levels of matrix metalloproteinase (MMP)-2 and urokinase plasminogen activator (uPA), and led to an obvious inhibition of both in vitro invasion and in vivo lung metastasis of A549 cells (P < 0.001). CONCLUSIONS: Our data demonstrate that OPN contributes to A549 cell metastasis by stimulating cell invasion, independent of cellular migration and proliferation. OPN could be a new treatment target of NSCLC.