Heparin co‐factor II enhances cell motility and promotes metastasis in non‐small cell lung cancer |
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| Authors: | Wei‐Yu Liao Chao‐Chi Ho Hsin‐Han Hou Tsi‐Hsuan Hsu Meng‐Feng Tsai Kuan‐Yu Chen Hsuan‐Yu Chen Yung‐Chie Lee Chong‐Jen Yu Pan‐Chyr Yang |
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| Affiliation: | 1. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan;2. Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan;3. Institute of Biophotonics, National Yang‐Ming University, Taipei, Taiwan;4. Department of Molecular Biotechnology, Da‐Yeh University, Chang‐Hua, Taiwan;5. Institute of Statistical Sciences, Academia Sinica, Taipei, Taiwan;6. Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan |
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| Abstract: | Using the Serial Analysis of Gene Expression (SAGE) database from the Cancer Genome Anatomy Project, we identified heparin co‐factor II (HCII), which is over‐expressed in non‐small cell lung cancer (NSCLC). Here, we investigated the clinical significance of HCII and provided molecular evidence to support the suggestion that HCII could enhance cancer metastasis in NSCLC. We found that high HCII expression in tumour tissue was associated with increased cancer recurrence and shorter overall survival times in 75 clinically operable NSCLC patients. High pretreatment plasma concentration of HCII was associated with reduced overall survival in 57 consecutive NSCLC patients. We over‐expressed and knocked down HCII expression in lung cancer cell lines and confirmed that HCII could promote cell motility, invasion ability and filopodium dynamics in NSCLC cells in vitro and increased metastatic colonization in an in vivo mouse model. Exogenous treatment of HCII promoted cancer cell migration, and this promigratory effect of HCII was independent of thrombin. We further showed that HCII could up‐regulate cancer cell migration through the activation of PI3K, which acts upstream of Rac1 and Cdc42, and this effect could be blocked by heparin. We suggest that HCII is a novel metastasis enhancer and may be used as a prognostic predictor for heparin treatment in NSCLC. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd |
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| Keywords: | heparin co‐factor II non‐small cell lung cancer cell motility metastasis |
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