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Interfacial geometry dictates cancer cell tumorigenicity

Nature Materials volume 15, pages 856–862 (2016)Cite this article

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Abstract

Within the heterogeneous architecture of tumour tissue there exists an elusive population of stem-like cells that are implicated in both recurrence and metastasis1,2. Here, by using engineered extracellular matrices, we show that geometric features at the perimeter of tumour tissue will prime a population of cells with a stem-cell-like phenotype. These cells show characteristics of cancer stem cells in vitro, as well as enhanced tumorigenicity in murine models of primary tumour growth and pulmonary metastases. We also show that interfacial geometry modulates cell shape, adhesion through integrin α5β1, MAPK and STAT activity, and initiation of pluripotency signalling. Our results for several human cancer cell lines suggest that interfacial geometry triggers a general mechanism for the regulation of cancer-cell state. Similar to how a growing tumour can co-opt normal soluble signalling pathways3, our findings demonstrate how cancer can also exploit geometry to orchestrate oncogenesis.

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Figure 1: Interfacial geometry at perimeter features directs expression of CSC markers.
Figure 2: Geometric cues activate CSCs at the perimeter through integrin α5β1, mitogen-activated protein kinase (MAPK) signalling and regulation of signal transducer and activator of transcription (STAT) pathways.
Figure 3: Cells encapsulated in model 3D microenvironments demonstrate interfacial regulation of the CSC phenotype.
Figure 4: Activated cells show higher tumorigenicity and metastatic potency in vivo.

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Acknowledgements

This research was supported with funding from the American Cancer Society Illinois Division Grant # 281225 and the National Science Foundation Grant # 1454616 CAR. Graduate student (K.L.W.) support was provided by Morris Animal Foundation. We thank the Beckman Institute ITG facilities, Institute of Genomic Biology Imaging facilities, Micro and Nanotechnology Laboratory facilities, and the Roy J. Carver Biotechnology Center.

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Authors and Affiliations

  1. Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA

    Junmin Lee, Amr A. Abdeen & Kristopher A. Kilian

  2. Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA

    Kathryn L. Wycislo

  3. Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA

    Timothy M. Fan

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  1. Junmin Lee
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Contributions

J.L. and K.A.K. conceived the ideas and designed the experiments. J.L., A.A.A., K.L.W. and T.M.F. conducted the experiments. J.L., A.A.A., K.L.W., T.M.F. and K.A.K. analysed the data. J.L., A.A.A., T.M.F. and K.A.K. interpreted the data and wrote the manuscript.

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Correspondence to Kristopher A. Kilian.

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The authors declare no competing financial interests.

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Lee, J., Abdeen, A., Wycislo, K. et al. Interfacial geometry dictates cancer cell tumorigenicity. Nature Mater 15, 856–862 (2016). https://doi.org/10.1038/nmat4610

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