title: 3D cell culture systems modeling tumor growth determinants in cancer target discovery.
abstract: Phenotypic heterogeneity of cancer cells, cell biological context, heterotypic crosstalk and the microenvironment are key determinants of the multistep process of tumor development. They sign responsible, to a significant extent, for the limited response and resistance of cancer cells to molecular-targeted therapies. Better functional knowledge of the complex intra- and intercellular signaling circuits underlying communication between the different cell types populating a tumor tissue and of the systemic and local factors that shape the tumor microenvironment is therefore imperative. Sophisticated 3D multicellular tumor spheroid (MCTS) systems provide an emerging tool to model the phenotypic and cellular heterogeneity as well as microenvironmental aspects of in vivo tumor growth. In this review we discuss the cellular, chemical and physical factors contributing to zonation and cellular crosstalk within tumor masses. On this basis, we further describe 3D cell culture technologies for growth of MCTS as advanced tools for exploring molecular tumor growth determinants and facilitating drug discovery efforts. We conclude with a synopsis on technological aspects for on-line analysis and post-processing of 3D MCTS models.
authors.affiliation: Institute of Molecular Health Sciences, ETH Zurich, 8093 Zurich, Switzerland. Electronic address: claudio.thoma@biol.ethz.ch.
authors.forename: Claudio R
authors.initials: CR
authors.lastname: Thoma
authors.affiliation: Institute of Molecular Health Sciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Miriam
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: InSphero AG, 8952 Schlieren, Switzerland.
authors.forename: Irina
authors.initials: I
authors.lastname: Agarkova
authors.affiliation: InSphero AG, 8952 Schlieren, Switzerland.
authors.forename: Jens M
authors.initials: JM
authors.lastname: Kelm
authors.affiliation: Institute of Molecular Health Sciences, ETH Zurich, 8093 Zurich, Switzerland. Electronic address: wilhelm.krek@biol.ethz.ch.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Krek
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018929:Cell Culture Techniques / Q000379:methods* / Q000639:trends; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D059016:Tumor Microenvironment / Q000187:drug effects / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents
keywords: 3D cell culture; Cancer cell signaling; Cisplatin (PubChem CID: 441203); Crizotinib (PubChem CID: 11626560); Doxorubicin (PubChem CID: 31703); Ethylene glycol (PubChem CID: 174); Imatinib (PubChem CID: 5291); Molecular cancer targets; Multicellular tumor spheroid (MCTS); Nitric oxide (PubChem CID: 145068); Oxygen (PubChem CID: 977); Pimonidazole (PubChem CID: 50981); Screening technology; Tumor microenvironment; Vemurafenib (PubChem CID: 42611257); ε-Caprolactone (PubChem CID: 10401)