title: Biomarkers for simplifying HTS 3D cell culture platforms for drug discovery: the case for cytokines.
abstract: In this review, we discuss the microenvironmental cues that modulate the status of cells to yield physiologically more relevant three-dimensional (3D) cell-based high throughput drug screening (HTS) platforms for drug discovery. Evidence is provided to support the view that simplifying 3D cell culture platforms for HTS applications calls for identifying and validating ubiquitous three-dimensionality biomarkers. Published results from avascular tumorigenesis and early stages of inflammatory wound healing, where cells transition from a two-dimensional (2D) to 3D microenvironment, conclusively report regulation by cytokines, providing the physiological basis for focusing on cytokines as potential three-dimensionality biomarkers. We discuss additional support for cytokines that comes from numerous 2D and 3D comparative transcriptomic and proteomic studies, which generally report upregulation of cytokines in 3D compared with 2D culture counterparts.
authors.affiliation: Cellular Bioengineering Laboratory, Faculty of Engineering, Driftmier Engineering Center, University of Georgia, Athens, GA 30602, USA.
authors.forename: Yinzhi
authors.initials: Y
authors.lastname: Lai
authors.forename: Amish
authors.initials: A
authors.lastname: Asthana
authors.forename: William S
authors.initials: WS
authors.lastname: Kisaalita
mesh_terms: D015415:Biomarkers; D018929:Cell Culture Techniques / Q000379:methods*; D016207:Cytokines / Q000378:metabolism*; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D057166:High-Throughput Screening Assays; D006801:Humans
chemical_list: D015415:Biomarkers; D016207:Cytokines