title: 3D tumor spheroid models for in vitro therapeutic screening: a systematic approach to enhance the biological relevance of data obtained.
abstract: The potential of a spheroid tumor model composed of cells in different proliferative and metabolic states for the development of new anticancer strategies has been amply demonstrated. However, there is little or no information in the literature on the problems of reproducibility of data originating from experiments using 3D models. Our analyses, carried out using a novel open source software capable of performing an automatic image analysis of 3D tumor colonies, showed that a number of morphology parameters affect the response of large spheroids to treatment. In particular, we found that both spheroid volume and shape may be a source of variability. We also compared some commercially available viability assays specifically designed for 3D models. In conclusion, our data indicate the need for a pre-selection of tumor spheroids of homogeneous volume and shape to reduce data variability to a minimum before use in a cytotoxicity test. In addition, we identified and validated a cytotoxicity test capable of providing meaningful data on the damage induced in large tumor spheroids of up to diameter in 650 μm by different kinds of treatments.
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Zanoni
authors.affiliation: Advanced Research Center on Electronic Systems for Information and Communication Technologies "E. De Castro" (ARCES), University of Bologna, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Piccinini
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Arienti
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Zamagni
authors.affiliation: Institute of Molecular Genetics, CNR-National Research Council of Italy, Bologna, Italy.|SC Laboratory of Musculoskeletal Cell Biology, Rizzoli Orthopedic Institute (IOR) IRCCS, Bologna, Italy.
authors.forename: Spartaco
authors.initials: S
authors.lastname: Santi
authors.affiliation: Radiotherapy Unit, IRST IRCCS, Meldola, Italy.
authors.forename: Rolando
authors.initials: R
authors.lastname: Polico
authors.affiliation: Advanced Research Center on Electronic Systems for Information and Communication Technologies "E. De Castro" (ARCES), University of Bologna, Italy.|Department of Computer Science and Engineering (DISI), University of Bologna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bevilacqua
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Tesei
mesh_terms: D048430:Cell Shape; D002470:Cell Survival; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D021621:Imaging, Three-Dimensional; D008954:Models, Biological; D015203:Reproducibility of Results; D018874:Spheroids, Cellular / Q000473:pathology*; D014407:Tumor Cells, Cultured