title: Circulating tumor cells from a 4-dimensional lung cancer model are resistant to cisplatin.
abstract: OBJECTIVE
  To determine the effect of cisplatin on circulatory tumor cells (CTC) and tumor nodules in a four-dimensional (4D) lung cancer model.
  
  
  METHODS
  CTCs from the 4D model seeded with H1299, A549, or H460 and respective cells that were grown under two-dimensional conditions in a Petri dish were treated with 50 μM cisplatin for 24 and 48 hours and cell viability was determined. The lung nodules in the 4D model were then treated with different continuous or intermittent doses of cisplatin and the nodule size, the number of CTCs, and the level of matrix metalloproteinase (MMP) were determined.
  
  
  RESULTS
  Cisplatin led to a significant decrease in the viability of tumor cells grown under 2D conditions (P < .01) but not in CTCs from the 4D model after both 24 hours and 48 hours. Cisplatin led to regression of tumor nodules with both the continuous and intermittent treatments. Moreover, there was a significantly higher number of CTCs per tumor area (P < .05) and MMP-2 production per tumor area (P = .007) for all human lung cancer cell lines grown in the 4D model when treated with cisplatin.
  
  
  CONCLUSIONS
  The 4D lung cancer model allows for the isolation of CTCs that are resistant to cisplatin treatment. The model may allow us to better understand the biology of cisplatin resistance.
authors.affiliation: Department of Surgery, Houston Methodist Research Institute, Houston, Tex.
authors.forename: Monika
authors.initials: M
authors.lastname: Vishnoi
authors.affiliation: Department of Surgery, Houston Methodist Research Institute, Houston, Tex.
authors.forename: Dhruva K
authors.initials: DK
authors.lastname: Mishra
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston, Tex.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thrall
authors.affiliation: Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Tex.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Kurie
authors.affiliation: Department of Surgery, Houston Methodist Research Institute, Houston, Tex; Department of Surgery, Weill Cornell Medical College, Houston Methodist Hospital, Houston, Tex. Electronic address: mpkim@houstonmethodist.org.
authors.forename: Min P
authors.initials: MP
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019149:Bioreactors; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D046509:Tissue Culture Techniques; D054457:Tissue Scaffolds
chemical_list: D000970:Antineoplastic Agents; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D002945:Cisplatin