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Engineering tumors with 3D scaffolds

Nature Methods volume 4, pages 855–860 (2007)Cite this article

Abstract

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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Figure 1: Characterization of tumor model.
Figure 2: Angiogenic characteristics.
Figure 3: Tumor growth in vivo from cells precultured in 2D and 3D.
Figure 4: Invasiveness and drug responsiveness.

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Acknowledgements

We thank K. Polyak (Dana Farber Cancer Institute) for her insightful review of this article, P. Kumar (University of Michigan) for helpful discussions, B. Tilton (Harvard University) for assistance with flow cytometry and Oxford Optronics for support with Oxylite measurements. Financial support was provided by the US National Institutes of Health (RO1 HL069957) and the Deutsche Forschungsgemeinschaft (post-doctoral fellowship to C.F.).

Author information

Authors and Affiliations

  1. School of Engineering and Applied Sciences, Harvard University, 40 Oxford Street

    Claudia Fischbach, Ruth Chen & David J Mooney

  2. Cambridge, 02138, Massachusetts, USA

    Claudia Fischbach, Ruth Chen & David J Mooney

  3. Department of Biomedical Engineering, Cornell University, 120 Olin Hall, Ithaca, 14853, New York, USA

    Claudia Fischbach

  4. Department of Oromaxillofacial Regeneration, Osaka University, 1-8 Yamada-oka Suita, Osaka, 565-0871, Japan

    Takuya Matsumoto

  5. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Tobias Schmelzle & Joan S Brugge

  6. School of Dentistry, University of Michigan, 1011 North University, Ann Arbor, 48109, Michigan, USA

    Peter J Polverini

Authors
  1. Claudia Fischbach
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  2. Ruth Chen
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  5. Joan S Brugge
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  7. David J Mooney
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Correspondence to David J Mooney.

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Supplementary Figures 1–7, Supplementary Methods (PDF 1273 kb)

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Fischbach, C., Chen, R., Matsumoto, T. et al. Engineering tumors with 3D scaffolds. Nat Methods 4, 855–860 (2007). https://doi.org/10.1038/nmeth1085

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