Nature Methods
- 4, 855 - 860 (2007)
Published online: 2 September 2007; | doi:10.1038/nmeth1085
Engineering tumors with 3D scaffoldsClaudia Fischbach1, 2, Ruth Chen1, Takuya Matsumoto3, Tobias Schmelzle4, Joan S Brugge4, Peter J Polverini5 & David J Mooney11
School of Engineering and Applied Sciences, Harvard University, 40 Oxford Street; Cambridge, Massachusetts 02138, USA. 2
Department of Biomedical Engineering, Cornell University, 120 Olin Hall, Ithaca, New York 14853, USA. 3
Osaka University, Department of Oromaxillofacial Regeneration, 1-8 Yamada-oka Suita, Osaka 565-0871, Japan. 4
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA. 5
School of Dentistry, University of Michigan, 1011 North University, Ann Arbor, Michigan 48109, USA.
Correspondence should be addressed to David J Mooney mooneyd@seas.harvard.edu Microenvironmental conditions control tumorigenesis and biomimetic culture systems that allow for in vitro and in vivo tumor modeling may greatly aid studies of cancer cells' dependency on these conditions. We engineered three-dimensional (3D) human tumor models using carcinoma cells in polymeric scaffolds that recreated microenvironmental characteristics representative of tumors in vivo. Strikingly, the angiogenic characteristics of tumor cells were dramatically altered upon 3D culture within this system, and corresponded much more closely to tumors formed in vivo. Cells in this model were also less sensitive to chemotherapy and yielded tumors with enhanced malignant potential. We assessed the broad relevance of these findings with 3D culture of other tumor cell lines in this same model, comparison with standard 3D Matrigel culture and in vivo experiments. This new biomimetic model may provide a broadly applicable 3D culture system to study the effect of microenvironmental conditions on tumor malignancy in vitro and in vivo.
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