title: Circulating tumor cells from 4D model have less integrin beta 4 expression.
abstract: BACKGROUND
  Currently, there is no in vitro or ex vivo model that can isolate circulating tumor cells (CTCs). Recently, we developed a four-dimensional (4D) lung cancer model that allows for the isolation of CTCs. We postulated that these cells have different properties than parental (2D) cells.
  
  
  METHODS
  We obtained CTCs by growing A549, H1299, 393P, and 344SQ cell lines on the 4D lung model. The CTCs were functionally characterized in vitro and gene expression of the cell adhesion molecules was compared with respective 2D cells. Integrin beta 4 (ITGB4) was further investigated by stably transfecting the A549 and H1299 cells.
  
  
  RESULTS
  We found that all cell lines produced CTCs, and that CTCs from the 4D model were less adherent to the plastic and have a slower growth rate than respective 2D cells (P < 0.01). Most of the cell adhesion molecules were downregulated (P < 0.05) in CTCs, and ITGB4 was the common molecule, significantly more underexpressed in CTCs from all cell lines than their respective 2D cells. The modulation of ITGB4 led to a differential function of 2D cells.
  
  
  CONCLUSIONS
  CTCs from the 4D model have different transcriptional, translational, and in vitro characteristics than the same cells grown on a petri dish, and these CTCs from the 4D model have the properties of CTCs that are responsible for metastasis.
authors.affiliation: Department of Surgery, Houston Methodist Research Institute, Houston, Texas.
authors.forename: Dhruva K
authors.initials: DK
authors.lastname: Mishra
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Scott
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardwell-Ozgo
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, 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; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D006801:Humans; D066298:In Vitro Techniques; D039663:Integrin beta4 / Q000378:metabolism*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D051381:Rats
chemical_list: D015815:Cell Adhesion Molecules; D039663:Integrin beta4; C013065:cell aggregation factors
keywords: 4D model; Circulating tumor cells; Ex vivo; Lung cancer