title: Role of fibulin-3 in lung cancer: in vivo and in vitro analyses.
abstract: Lung cancer was the most commonly diagnosed cancer in 2008 worldwide. The level of fibulin-3 expression was found to be decreased in many cancer types due to aberrant promoter methylation and is correlated with poor survival of patients. However, the role of fibulin-3 and which form of fibulin-3 is expressed in lung cancer cells remain unclear. Therefore, pathologic and functional studies were carried out to determine the role of fibulin-3 in suppressing lung cancer both in vivo and in vitro. In the present study, we found that the levels of fibulin-3 mRNA and protein were lower in cancer tissues than in normal tissues. Downregulation of fibulin-3 mRNA in tumor tissues was associated with an increase in fibulin-3 promoter methylation. Circulating fibulin-3 was significantly associated with tumor progression, survival rate of lung cancer patients, and the number of circulating tumor cells (CTCs). To examine the effects of exogenous expression of fibulin-3 in vitro, lung cancer A549 cells were transfected with the pEGFP-C1-fibulin-3 expression vector. Relative to the untreated cells, fibulin-3-expressing cells exhibited lower proliferation and mobility as determined by MTT and Transwell assays, respectively. To conclude, our results suggest that fibulin-3 negatively modulates the invasiveness of lung cancer cells via regulation of p38-MAPK and MMP-2/9.
authors.affiliation: Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, P.R. China.
authors.forename: Shun
authors.initials: S
authors.lastname: Xu
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Yan-Bin
authors.initials: YB
authors.lastname: Sun
authors.forename: Hao-You
authors.initials: HY
authors.lastname: Wang
authors.forename: Chang-Bo
authors.initials: CB
authors.lastname: Sun
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D019175:DNA Methylation; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009360:Neoplastic Cells, Circulating; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D015996:Survival Rate; D014162:Transfection; D014945:Wound Healing / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics
chemical_list: C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9