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Cancers 2018, 10(8), 265; https://doi.org/10.3390/cancers10080265

Organotypic 3D Models of the Ovarian Cancer Tumor Microenvironment

1
Department of Chemistry, University of Chicago, Chicago, IL 60637, USA
2
Department of Obstetrics and Gynecology, Section of Gynecologic Oncology, University of Chicago, Chicago, IL 60637, USA
*
Author to whom correspondence should be addressed.
Received: 19 June 2018 / Revised: 3 August 2018 / Accepted: 8 August 2018 / Published: 9 August 2018
(This article belongs to the Special Issue The Tumor Microenvironment of High Grade Serous Ovarian Cancer)
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Abstract

Ovarian cancer progression involves multifaceted and variable tumor microenvironments (TMEs), from the in situ carcinoma in the fallopian tube or ovary to dissemination into the peritoneal cavity as single cells or spheroids and attachment to the mesothelial-lined surfaces of the omentum, bowel, and abdominal wall. The TME comprises the tumor vasculature and lymphatics (including endothelial cells and pericytes), in addition to mesothelial cells, fibroblasts, immune cells, adipocytes and extracellular matrix (ECM) proteins. When generating 3D models of the ovarian cancer TME, researchers must incorporate the most relevant stromal components depending on the TME in question (e.g., early or late disease). Such complexity cannot be captured by monolayer 2D culture systems. Moreover, immortalized stromal cell lines, such as mesothelial or fibroblast cell lines, do not always behave the same as primary cells whose response in functional assays may vary from donor to donor; 3D models with primary stromal cells may have more physiological relevance than those using stromal cell lines. In the current review, we discuss the latest developments in organotypic 3D models of the ovarian cancer early metastatic microenvironment. Organotypic culture models comprise two or more interacting cell types from a particular tissue. We focus on organotypic 3D models that include at least one type of primary stromal cell type in an ECM background, such as collagen or fibronectin, plus ovarian cancer cells. We provide an overview of the two most comprehensive current models—a 3D model of the omental mesothelium and a microfluidic model. We describe the cellular and non-cellular components of the models, the incorporation of mechanical forces, and how the models have been adapted and utilized in functional assays. Finally, we review a number of 3D models that do not incorporate primary stromal cells and summarize how integration of current models may be the next essential step in tackling the complexity of the different ovarian cancer TMEs. View Full-Text
Keywords: ovarian cancer; tumor microenvironment; 3D models ovarian cancer; tumor microenvironment; 3D models
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Watters, K.M.; Bajwa, P.; Kenny, H.A. Organotypic 3D Models of the Ovarian Cancer Tumor Microenvironment. Cancers 2018, 10, 265.

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