Incorporation of multicellular spheroids into 3‐D polymeric scaffolds provides an improved tumor model for screening anticancer drugs

• Published in: Cancer science Vol. 101; no. 12; pp. 2637 - 2643
• Main Authors: Ho, Won Jin, Pham, Edward A., Kim, Jun W., Ng, Christopher W., Kim, Jae H., Kamei, Daniel T., Wu, Benjamin M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2010; Blackwell
• Subjects: Biological and medical sciences; Drug Screening Assays, Antitumor - methods; Humans; Medical sciences; Original; Spheroids, Cellular - cytology; Spheroids, Cellular - drug effects; Tissue Scaffolds; Tumor Cells, Cultured - cytology; Tumor Cells, Cultured - drug effects; Tumors; Antineoplastic agent; Drug; Incorporation; Cancerology; Tumor; Models; Spheroid; Medical screening
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/j.1349-7006.2010.01723.x

Development of cancer therapeutics requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Three‐dimensional (3‐D) in vitro models have therefore been investigated for drug screening. In this study, we have developed a novel in vitro model in which multicellular aggregates, or spheroids, were incorporated into 3‐D porous scaffolds. Drug resistance assays showed that spheroid‐seeded scaffolds have much higher drug resistance than monolayer cultures, spheroids on flat substrates, or scaffolds seeded with dispersed cells. Furthermore, spheroid‐seeded scaffolds demonstrated higher lactate production leading to acidosis, and higher expression of angiogenic factors. These data suggest that the spheroid‐seeded 3‐D scaffolds might serve as a useful in vitro system for screening cancer therapeutics. (Cancer Sci 2010; 101: 2637–2643)