title: Osteopontin as a potential biomarker of proliferation and invasiveness for lung cancer.
abstract: OBJECTIVE
  Lung cancer is one of the most malignant tumors and poses a significant threat to human health. Osteopontin (OPN) is a variably expressed, secreted glycophosphoprotein that mediates the growth and metastases of several carcinoma types. In this study, we aimed to understand the role of OPN in lung cancer cell proliferation and invasiveness.
  
  
  METHODS
  Expression of OPN was examined using an immunohistochemical method in paraffin-embedded sections collected from 49 patients with lung cancer. We silenced OPN expression by lentivirus-mediated OPN-specific small interfering RNA (siRNA) and examined the proliferation and invasiveness of OPN-silenced lung cancer cell (A549) through MTT, BrdU, flow cytometry, and Matrigel assay. In addition, we tested the role of individual OPN splice variants in A549 cell growth and invasion by constructing OPN overexpression lentiviruses.
  
  
  RESULTS
  Downregulation of OPN inhibited A549 cell proliferation and in vivo tumor growth, abrogated augmentation of invasion, induced G1-phase cell cycle arrest, and induced cell late apoptosis and necrosis. Moreover, the proliferation and invasiveness was linked to different OPN splice variants, of which OPN-b affected the cell proliferation and OPN-c showed significant correlation with invasion behavior.
  
  
  CONCLUSIONS
  Our data suggested that OPN served as a potential biomarker for invasive lung cancer and provided new molecular-targeted therapy for lung cancer based on lentivirus-mediated RNA interference.
authors.affiliation: Department of Urology Surgery, The Second Affiliated Hospital of Harbin Medical University, 150081, Harbin, China.
authors.forename: Bai
authors.initials: B
authors.lastname: Zhao
authors.forename: Tiemin
authors.initials: T
authors.lastname: Sun
authors.forename: Fanjuan
authors.initials: F
authors.lastname: Meng
authors.forename: Aibing
authors.initials: A
authors.lastname: Qu
authors.forename: Chunling
authors.initials: C
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Yu
authors.initials: Y
authors.lastname: Jin
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D053495:Osteopontin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053495:Osteopontin