title: A Model for Spheroid versus Monolayer Response of SK-N-SH Neuroblastoma Cells to Treatment with 15-Deoxy-PGJ2.
abstract: Researchers have observed that response of tumor cells to treatment varies depending on whether the cells are grown in monolayer, asin vitrospheroids orin vivo. This study uses data from the literature on monolayer treatment of SK-N-SH neuroblastoma cells with 15-deoxy-PGJ2and couples it with data on growth rates for untreated SK-N-SH neuroblastoma cells grown as multicellular spheroids. A linear model is constructed for untreated and treated monolayer data sets, which is tuned to growth, death, and cell cycle data for the monolayer case for both control and treatment with 15-deoxy-PGJ2. The monolayer model is extended to a five-dimensional nonlinear model ofin vitrotumor spheroid growth and treatment that includes compartments of the cell cycle (G1,S,G2/M) as well as quiescent (Q) and necrotic (N) cells. Monolayer treatment data for 15-deoxy-PGJ2is used to derive a prediction of spheroid response under similar treatments. For short periods of treatment, spheroid response is less pronounced than monolayer response. The simulations suggest that the difference in response to treatment of monolayer versus spheroid cultures observed in laboratory studies is a natural consequence of tumor spheroid physiology rather than any special resistance to treatment.
authors.affiliation: Department of Mathematics, HB 6188, Dartmouth College, Hanover, NH 03768, USA.
authors.forename: Dorothy I
authors.identifier: 0000-0002-9356-8353
authors.initials: DI
authors.lastname: Wallace
authors.affiliation: Department of Mathematics, HB 6188, Dartmouth College, Hanover, NH 03768, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Dunham
authors.affiliation: Department of Mathematics, HB 6188, Dartmouth College, Hanover, NH 03768, USA.
authors.forename: Paula X
authors.initials: PX
authors.lastname: Chen
authors.affiliation: Department of Mathematics, HB 6188, Dartmouth College, Hanover, NH 03768, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Mathematics, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Milan
authors.initials: M
authors.lastname: Huynh
authors.affiliation: Department of Mathematics, HB 6188, Dartmouth College, Hanover, NH 03768, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Rheingold
authors.affiliation: Department of Mathematics, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: Prosper
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D009447:Neuroblastoma / Q000188:drug therapy*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018874:Spheroids, Cellular / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; C037112:9-deoxy-delta-9-prostaglandin D2; D015230:Prostaglandin D2