title: Modeling Ewing sarcoma tumors in vitro with 3D scaffolds.
abstract: The pronounced biological influence of the tumor microenvironment on cancer progression and metastasis has gained increased recognition over the past decade, yet most preclinical antineoplastic drug testing is still reliant on conventional 2D cell culture systems. Although monolayer cultures recapitulate some of the phenotypic traits observed clinically, they are limited in their ability to model the full range of microenvironmental cues, such as ones elicited by 3D cell-cell and cell-extracellular matrix interactions. To address these shortcomings, we established an ex vivo 3D Ewing sarcoma model that closely mimics the morphology, growth kinetics, and protein expression profile of human tumors. We observed that Ewing sarcoma cells cultured in porous 3D electrospun poly(ε-caprolactone) scaffolds not only were more resistant to traditional cytotoxic drugs than were cells in 2D monolayer culture but also exhibited remarkable differences in the expression pattern of the insulin-like growth factor-1 receptor/mammalian target of rapamycin pathway. This 3D model of the bone microenvironment may have broad applicability for mechanistic studies of bone sarcomas and exhibits the potential to augment preclinical evaluation of antineoplastic drug candidates for these malignancies.
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77005, USA.
authors.forename: Eliza Li Shan
authors.initials: EL
authors.lastname: Fong
authors.forename: Salah-Eddine
authors.initials: SE
authors.lastname: Lamhamedi-Cherradi
authors.forename: Emily
authors.initials: E
authors.lastname: Burdett
authors.forename: Vandhana
authors.initials: V
authors.lastname: Ramamoorthy
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Lazar
authors.forename: F Kurtis
authors.initials: FK
authors.lastname: Kasper
authors.forename: Mary C
authors.initials: MC
authors.lastname: Farach-Carson
authors.forename: Deeksha
authors.initials: D
authors.lastname: Vishwamitra
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Demicco
authors.forename: Brian A
authors.initials: BA
authors.lastname: Menegaz
authors.forename: Hesham M
authors.initials: HM
authors.lastname: Amin
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Ludwig
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000503:physiopathology* / Q000648:ultrastructure; D002208:Caproates; D045744:Cell Line, Tumor; D019295:Computational Biology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007783:Lactones; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D008855:Microscopy, Electron, Scanning; D017451:Receptors, Somatomedin / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000503:physiopathology* / Q000648:ultrastructure; D046509:Tissue Culture Techniques / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D002208:Caproates; D007783:Lactones; D017451:Receptors, Somatomedin; C121056:caprolactone