title: An imaging-based platform for high-content, quantitative evaluation of therapeutic response in 3D tumour models.
abstract: While it is increasingly recognized that three-dimensional (3D) cell culture models recapitulate drug responses of human cancers with more fidelity than monolayer cultures, a lack of quantitative analysis methods limit their implementation for reliable and routine assessment of emerging therapies. Here, we introduce an approach based on computational analysis of fluorescence image data to provide high-content readouts of dose-dependent cytotoxicity, growth inhibition, treatment-induced architectural changes and size-dependent response in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of clinically relevant cytotoxic modalities and appropriately designed controls for reliable quantification of fluorescence signal. This streamlined methodology reads out the high density of information embedded in 3D culture systems, while maintaining a level of speed and efficiency traditionally achieved with global colorimetric reporters in order to facilitate broader implementation of 3D tumour models in therapeutic screening.
authors.affiliation: 1] Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, U.S.A. [2] Department of Physics, University of Massachusetts Boston, Boston, MA, U.S.A.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Celli
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, U.S.A.
authors.forename: Imran
authors.initials: I
authors.lastname: Rizvi
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, U.S.A.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Blanden
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, U.S.A.
authors.forename: Iqbal
authors.initials: I
authors.lastname: Massodi
authors.affiliation: 1] Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, U.S.A. [2] Department of Physics, University of Massachusetts Boston, Boston, MA, U.S.A.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Glidden
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH, U.S.A.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Pogue
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, U.S.A.
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D057166:High-Throughput Screening Assays; D006801:Humans; D051379:Mice; D008853:Microscopy; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents