Cell Reports
Volume 26, Issue 3, 15 January 2019, Pages 608-623.e6
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Article
Modeling Tumor Phenotypes In Vitro with Three-Dimensional Bioprinting

https://doi.org/10.1016/j.celrep.2018.12.090Get rights and content
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Highlights

  • Bioprinted tumor tissue is a scaffold-free model of tumor-stromal interactions

  • Cells within bioprinted tissues mature, self-organize, and deposit matrix proteins

  • Heterogeneity in therapeutic response, migration, and signaling can be assessed

  • Primary patient tissue can be bioprinted into tissues for translational studies

Summary

The tumor microenvironment plays a critical role in tumor growth, progression, and therapeutic resistance, but interrogating the role of specific tumor-stromal interactions on tumorigenic phenotypes is challenging within in vivo tissues. Here, we tested whether three-dimensional (3D) bioprinting could improve in vitro models by incorporating multiple cell types into scaffold-free tumor tissues with defined architecture. We generated tumor tissues from distinct subtypes of breast or pancreatic cancer in relevant microenvironments and demonstrate that this technique can model patient-specific tumors by using primary patient tissue. We assess intrinsic, extrinsic, and spatial tumorigenic phenotypes in bioprinted tissues and find that cellular proliferation, extracellular matrix deposition, and cellular migration are altered in response to extrinsic signals or therapies. Together, this work demonstrates that multi-cell-type bioprinted tissues can recapitulate aspects of in vivo neoplastic tissues and provide a manipulable system for the interrogation of multiple tumorigenic endpoints in the context of distinct tumor microenvironments.

Keywords

tumor microenvironment
three-dimensional bioprinting
breast cancer
pancreatic cancer
3D tumor models

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These authors contributed equally

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