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Cell Rep. 2019 Jan 15;26(3):608-623.e6. doi: 10.1016/j.celrep.2018.12.090.

Modeling Tumor Phenotypes In Vitro with Three-Dimensional Bioprinting.

Author information

1
Department of Medical and Molecular Genetics, Oregon Health & Science University, Portland, OR 97201, USA.
2
Tissue Applications, Organovo, Inc., San Diego, CA 92121, USA.
3
Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97239, USA.
4
Department of Surgery, Oregon Health & Science University, Portland, OR 97239, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA.
5
Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97239, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA.
6
Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97239, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA; OHSU Center for Spatial Systems Biomedicine, Oregon Health & Science University, Portland, OR 97201, USA.
7
Department of Medical and Molecular Genetics, Oregon Health & Science University, Portland, OR 97201, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA. Electronic address: searsr@ohsu.edu.

Abstract

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:

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

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