title: 3D Models of the NCI60 Cell Lines for Screening Oncology Compounds.
abstract: The NCI60 cell line panel screen includes 60 human tumor cell lines derived from nine tumor types that has been used over the past 20+ years to screen small molecules, biologics, and natural products for activity. Cells in monolayer culture in 96-well plates are exposed to compounds for 48 h, and Sulforhodamine B is used to determine cell viability. Data analysis tools such as COMPARE allow classification of compounds based on the pattern of cell line response. However, many compounds highly active in monolayer cell culture fail to show efficacy in vivo. Therefore, we explored 3D culture of the NCI60 panel as a strategy to improve the predictive accuracy of the screen. 3D cultures more closely resemble tumors than monolayer cultures with tighter cell-cell contact and nutrient and oxygen gradients between the periphery and the center. We optimized the NCI60 cell line panel for generating 3D spheroids of a prespecified diameter (300-500 µm) in ultra-low attachment (ULA) plates. Spheroids were classified into four categories based on imaging, and concentration response of select agents in 2D and 3D models is presented.
authors.affiliation: 1 Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Lab for Cancer Research, Frederick, MD, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Selby
authors.affiliation: 1 Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Lab for Cancer Research, Frederick, MD, USA.
authors.forename: Rene
authors.initials: R
authors.lastname: Delosh
authors.affiliation: 1 Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Lab for Cancer Research, Frederick, MD, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Laudeman
authors.affiliation: 1 Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Lab for Cancer Research, Frederick, MD, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Ogle
authors.affiliation: 1 Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Lab for Cancer Research, Frederick, MD, USA.
authors.forename: Russell
authors.initials: R
authors.lastname: Reinhart
authors.affiliation: 1 Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Lab for Cancer Research, Frederick, MD, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Silvers
authors.affiliation: 1 Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Lab for Cancer Research, Frederick, MD, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Lawrence
authors.affiliation: 1 Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Lab for Cancer Research, Frederick, MD, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Kinders
authors.affiliation: 1 Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Lab for Cancer Research, Frederick, MD, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Parchment
authors.affiliation: 2 Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Teicher
authors.affiliation: 1 Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Lab for Cancer Research, Frederick, MD, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques / Q000379:methods; D045744:Cell Line, Tumor / Q000166:cytology* / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents
keywords: 3D; NCI60 cells; ULA plates; cell culture; spheroids