In Vitro Modeling of the Tumor Microenvironment in Tumor Organoids

Abstract

Background: The tumor microenvironment (TME) represents the many components occupying the space within and surrounding a tumor, including cells, signaling factors, extracellular matrix, and vasculature. Each component has the potential to assume many forms and functions which in turn contribute to the overall state of the TME, and further contribute to the progression and disposition of the tumor itself. The sum of these components can drive a tumor towards progression, keep a migratory tumor at bay, or even control chemotherapeutic response. The wide potential for interaction that the TME is an integral part of a tumor's ecosystem, and it is imperative to include it when studying and modeling cancer in vitro. Fortunately, the development of tissue engineering and biofabrication technologies and methodologies have allowed widespread inclusion of TME-based factors into in vitro tissue-equivalent models.

Methods: In this review, we compiled contemporary literature sources to provide an overview of the field of TME models, ranging from simple to complex.

Results: We have identified important components of the TME, how they can be included in in vitro study, and cover examples across a range of cancer types.

Conclusion: Our goal with this text is to provide a foundation for prospective research into the TME.

Keywords: Cancer; Microenvironment; Organoids; Preclinical models.

Fig. 1

The components of the tumor microenvironment. The TME is composed of many different cell types, signaling factors, extracellular matrix components and vasculature. They each interact with one another which in turn drives tumor disposition in a dynamic, multi-variate process

Fig. 2

3D culture modalities. A–C There are many types of culture formats which can be combined, tuned, and adapted to produce a final model or organoid that fits the study at hand. Generally, techniques can be separated into several types: (1) membrane-based typically used for lung, gut, and other luminal tissue models, (2) hydrogel encapsulated systems which can be adapted to all tumor types, and (3) aggregation technologies most suited to solid tumor models