title: Heparin co-factor II enhances cell motility and promotes metastasis in non-small cell lung cancer.
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.
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Liao
authors.forename: Chao-Chi
authors.initials: CC
authors.lastname: Ho
authors.forename: Hsin-Han
authors.initials: HH
authors.lastname: Hou
authors.forename: Tsi-Hsuan
authors.initials: TH
authors.lastname: Hsu
authors.forename: Meng-Feng
authors.initials: MF
authors.lastname: Tsai
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Chen
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Chen
authors.forename: Yung-Chie
authors.initials: YC
authors.lastname: Lee
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.forename: Chau-Hwang
authors.initials: CH
authors.lastname: Lee
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D015844:Heparin Cofactor II / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics
chemical_list: C047932:SERPIND1 protein, human; D015844:Heparin Cofactor II; D019869:Phosphatidylinositol 3-Kinases
keywords: cell motility; heparin co-factor II; metastasis; non-small cell lung cancer