title: From competency to dormancy: a 3D model to study cancer cells and drug responsiveness.
abstract: BACKGROUND
  The heterogeneous and dynamic tumor microenvironment has significant impact on cancer cell proliferation, invasion, drug response, and is probably associated with entering dormancy and recurrence. However, these complex settings are hard to recapitulate in vitro.
  
  
  METHODS
  In this study, we mimic different restriction forces that tumor cells are exposed to using a physiologically relevant 3D model with tunable mechanical stiffness.
  
  
  RESULTS
  Breast cancer MDA-MB-231, colon cancer HCT-116 and pancreatic cancer CFPAC cells embedded in the stiffer gels exhibit a changed morphology and cluster formation, prolonged doubling time, and a slower metabolism rate, recapitulating the pathway from competency to dormancy. Altering environmental restriction allows them to re-enter and exit dormant conditions and change their sensitivities to drugs such as paclitaxol and gemcitabine. Cells surviving drug treatments can still regain competent growth and form tumors in vivo.
  
  
  CONCLUSIONS
  We have successfully developed an in vitro 3D model to mimic the effects of matrix restriction on tumor cells and this high throughput model can be used to study tumor cellular functions and their drug responses in their different states. This all in one platform may aid effective drug development.
authors: Nimni-Cordoba Tissue Engineering and Drug Discovery Laboratory, Division of Plastic and Reconstructive Surgery, Departments of Surgery and Biomedical Engineering, Keck School of Medicine, University of Southern California, 1333 San Pablo St., BMT 302, Los Angeles, CA, 90089, USA. josephy@usc.edu.
authors: Josephine Y
authors: JY
authors: Fang
authors: Nimni-Cordoba Tissue Engineering and Drug Discovery Laboratory, Division of Plastic and Reconstructive Surgery, Departments of Surgery and Biomedical Engineering, Keck School of Medicine, University of Southern California, 1333 San Pablo St., BMT 302, Los Angeles, CA, 90089, USA. shihjyet@usc.edu.
authors: Shih-Jye
authors: SJ
authors: Tan
authors: Nimni-Cordoba Tissue Engineering and Drug Discovery Laboratory, Division of Plastic and Reconstructive Surgery, Departments of Surgery and Biomedical Engineering, Keck School of Medicine, University of Southern California, 1333 San Pablo St., BMT 302, Los Angeles, CA, 90089, USA. yichenwu@usc.edu.
authors: Yi-Chen
authors: YC
authors: Wu
authors: Nimni-Cordoba Tissue Engineering and Drug Discovery Laboratory, Division of Plastic and Reconstructive Surgery, Departments of Surgery and Biomedical Engineering, Keck School of Medicine, University of Southern California, 1333 San Pablo St., BMT 302, Los Angeles, CA, 90089, USA. zyang@usc.edu.
authors: Zhi
authors: Z
authors: Yang
authors: Nimni-Cordoba Tissue Engineering and Drug Discovery Laboratory, Division of Plastic and Reconstructive Surgery, Departments of Surgery and Biomedical Engineering, Keck School of Medicine, University of Southern California, 1333 San Pablo St., BMT 302, Los Angeles, CA, 90089, USA. baxuanho@usc.edu.
authors: Ba X
authors: BX
authors: Hoang
authors: Nimni-Cordoba Tissue Engineering and Drug Discovery Laboratory, Division of Plastic and Reconstructive Surgery, Departments of Surgery and Biomedical Engineering, Keck School of Medicine, University of Southern California, 1333 San Pablo St., BMT 302, Los Angeles, CA, 90089, USA. bohan@usc.edu.
authors: Bo
authors: B
authors: Han
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008819:Mice, Nude; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D059016:Tumor Microenvironment / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents