title: Ex vivo four-dimensional lung cancer model mimics metastasis.
abstract: BACKGROUND
  We have developed a four-dimensional (4D) lung cancer model that forms perfusable tumor nodules. We determined if the model could be modified to mimic metastasis.
  
  
  METHODS
  We modified the 4D lung cancer model by seeding H1299, A549, or H460 cells through the trachea only to the left lobes of the acellular lung matrix. The model was modified so that the tumor cells can reach the right lobes of the acellular lung matrix only through the pulmonary artery as circulating tumor cells (CTC). We determined the gene expressions of the primary tumor, CTCs, and metastatic lesions using the Human OneArray chip.
  
  
  RESULTS
  All cell lines formed a primary tumor in the left lobe of the ex vivo 4D lung cancer model. The CTCs were identified in the media and increased over time. All cell lines formed metastatic lesions with H460 forming significantly more metastatic lesions than H1299 and A549 cells. The CTC gene signature predicted poor survival in lung cancer patients. Unique genes were significantly expressed in CTC compared with the primary tumor and metastatic lesion.
  
  
  CONCLUSIONS
  The 4D lung cancer model can isolate tumor cells in 3 phases of tumor progression. This 4D lung cancer model may mimic the biology of lung cancer metastasis and may be used to determine its mechanism and potential therapy in the future.
authors.affiliation: Department of Surgery, Houston Methodist Research Institute, Houston, Texas.
authors.forename: Dhruva K
authors.initials: DK
authors.lastname: Mishra
authors.affiliation: Division of Biostatistics, Dan L. Duncan Cancer Center, Houston, Texas; Department of Medicine, Baylor College of Medicine, Houston, Texas.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.affiliation: Division of Biostatistics, Dan L. Duncan Cancer Center, Houston, Texas.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Biostatistics, Dan L. Duncan Cancer Center, Houston, Texas.
authors.forename: Fengju
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thrall
authors.affiliation: Department of Surgery, Houston Methodist Research Institute, Houston, Texas; Department of Surgery, Weill Cornell Medical College, Houston Methodist Hospital, Houston, Texas. Electronic address: mpkim@houstonmethodist.org.
authors.forename: Min P
authors.initials: MP
authors.lastname: Kim
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D045744:Cell Line, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary*; D023421:Models, Animal; D008954:Models, Biological; D009360:Neoplastic Cells, Circulating; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity