title: Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D.
abstract: BACKGROUND
  MultiCellular Tumor Spheroid (MCTS) mimics the organization of a tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. Here we report how the characteristics of MCTS in association with new technological developments can be used to explore the regionalization and the activation of cell cycle checkpoints in 3D.
  
  
  METHODS
  Cell cycle and proliferation parameters were investigated in Capan-2 spheroids by immunofluorescence staining, EdU incorporation and using cells engineered to express Fucci-red and -green reporters.
  
  
  RESULTS
  We describe in details the changes in proliferation and cell cycle parameters during spheroid growth and regionalization. We report the kinetics and regionalized aspects of cell cycle arrest in response to checkpoint activation induced by EGF starvation, lovastatin treatment and etoposide-induced DNA damage.
  
  
  CONCLUSIONS
  Our data present the power and the limitation of spheroids made of genetically modified cells to explore cell cycle checkpoints. This study paves the way for the investigation of molecular aspects and dynamic studies of the response to novel antiproliferative agents in 3D models.
authors: Université de Toulouse; ITAV-USR3505, Toulouse F-31106, France.
authors: Jennifer
authors: J
authors: Laurent
authors: Céline
authors: C
authors: Frongia
authors: Martine
authors: M
authors: Cazales
authors: Odile
authors: O
authors: Mondesert
authors: Bernard
authors: B
authors: Ducommun
authors: Valérie
authors: V
authors: Lobjois
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D003603:Cytotoxins / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D008954:Models, Biological; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology*; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003603:Cytotoxins; D003841:Deoxycytidine; D000093542:Gemcitabine
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