title: Integrative analyses identify osteopontin, LAMB3 and ITGB1 as critical pro-metastatic genes for lung cancer.
abstract: OBJECTIVE
  To explore the key regulatory genes associated with lung cancer in order to reduce its occurrence and progress through silencing these key genes.
  
  
  METHODS
  To identify the key regulatory genes involved in lung cancer, we performed a combination of gene array and bioinformatics analyses to compare gene transcription profiles in 3 monoclonal cell strains with high, medium or low metastatic abilities, which were separated from the SPC-A-1sci and SPC-A-1 cell lines by limiting dilution monoclone assay. We then analyzed those genes' biological activities by knocking down their expression in SPC-A-1sci cells using siRNA and lenti-viral shRNA vectors, followed by determinations of the invasion and migration capabilities of the resulting cell lines in vitro as well as their potential for inducing occurrence and metastasis of lung cancer in vivo. To examine the clinical relevance of these findings, we analyzed the expression levels of the identified genes in human lung cancer tissues (n = 135) and matched adjacent normal tissues by immunohistochemical (IHC) staining.
  
  
  RESULTS
  Three monoclonal cell strains characterized with high, medium or low metastatic abilities were successfully selected. Gene array and bioinformatics analyses implied that osteopontin, LAMB3 and ITGB1 were key genes involved in lung cancer. Knockdown of these genes suppressed human lung cancer cell invasion and metastasis in vitro and in vivo. Clinical sample analyses indicated that osteopontin, LAMB3 and ITGB1 protein expression levels were higher in lung cancer patients, compared to non-cancerous adjacent tissues, and correlated with lymphatic metastasis.
  
  
  CONCLUSIONS
  We confirmed that osteopontin, LAMB3 and ITGB1 played important roles in the occurrence and metastasis of lung cancer, thus provided important clues to understanding the molecular mechanism of metastasis and contributing to the therapeutic treatment of lung cancer.
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Xiao-Min
authors: XM
authors: Wang
authors: Jing
authors: J
authors: Li
authors: Ming-Xia
authors: MX
authors: Yan
authors: Lei
authors: L
authors: Liu
authors: De-Shui
authors: DS
authors: Jia
authors: Qin
authors: Q
authors: Geng
authors: He-Chun
authors: HC
authors: Lin
authors: Xiang-Huo
authors: XH
authors: He
authors: Jin-Jun
authors: JJ
authors: Li
authors: Ming
authors: M
authors: Yao
mesh_terms: D000368:Aged; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D053495:Osteopontin / Q000235:genetics*; D034622:RNA Interference; D014162:Transfection; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D019012:Integrin beta1; D053495:Osteopontin; D000097794:Kalinin