Modeling Ewing sarcoma tumors in vitro with 3D scaffolds

Eliza Li Shan Fong, Salah Eddine Lamhamedi-Cherradi, Emily Burdett, Vandhana Ramamoorthy, Alexander J. Lazar, F. Kurtis Kasper, Mary C. Farach-Carson, Deeksha Vishwamitra, Elizabeth G. Demicco, Brian A. Menegaz, Hesham M. Amin, Antonios G. Mikos, Joseph A. Ludwig

Research output: Contribution to journalArticlepeer-review

194 Scopus citations

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(e-cap-rolactone) scaffolds not only were more resistant to traditional cy-totoxic 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 rapamy-cin 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 an-tineoplastic drug candidates for these malignancies.

Original languageEnglish (US)
Pages (from-to)6500-6505
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number16
DOIs
StatePublished - Apr 16 2013

ASJC Scopus subject areas

  • General

MD Anderson CCSG core facilities

  • Advanced Technology Genomics Core
  • Bioinformatics Shared Resource
  • Functional Proteomics Reverse Phase Protein Array Core
  • Research Animal Support Facility
  • Cytogenetics and Cell Authentication Core

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