Abstract

Simple SummaryTumor stroma is known to significantly influence cancer initiation and progression. In the last decade, 3D cell cultures have shown potential in modeling the tumor microenvironment. This review summarizes the main features of current 3D models, shedding light on their importance in the study of cancer biology and treatment.It is now well established that the tumor microenvironment plays a key role in determining cancer growth, metastasis and drug resistance. Thus, it is fundamental to understand how cancer cells interact and communicate with their stroma and how this crosstalk regulates disease initiation and progression. In this setting, 3D cell cultures have gained a lot of interest in the last two decades, due to their ability to better recapitulate the complexity of tumor microenvironment and therefore to bridge the gap between 2D monolayers and animal models. Herein, we present an overview of the 3D systems commonly used for studying tumor–stroma interactions, with a focus on recent advances in cancer modeling and drug discovery and testing.

Highlights

  • The tumor stroma is composed of extracellular matrix (ECM) and various nonmalignant cell types, including endothelial, mesenchymal and immune cells [1,2]

  • This review summarizes the main characteristics of the 3D models currently employed in the study of tumor–stroma communication: the pros and cons of each technique are discussed, followed by an extensive overview of the major findings obtained through these methods in the field of cancer research

  • Due to the increasing interest of the scientific community in the characterization of tumor microenvironment, the present manuscript aims at offering a selection of recent literature illustrating novel approaches for the production and use of 3D cell cultures in the analysis of tumor interactions with ECM, blood vessels, mesenchymal cells and immune system

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Summary

Introduction

The tumor stroma is composed of extracellular matrix (ECM) and various nonmalignant cell types, including endothelial, mesenchymal (e.g., fibroblasts and adipocytes) and immune (e.g., lymphocytes, monocytes and neutrophils) cells [1,2]. These cells communicate with each other and with the tumor mass, by secreting a variety of molecules that affect tumor behavior through different signaling pathways [3,4]. Vascular endothelial growth factor (VEGF), have been widely recognized as master regulators of the interactions occurring within the tumor microenvironment [5] In addition to these polypeptides, cytokines, extracellular vesicles and miRNAs play a pivotal role in the control of cell–cell communication [6,7,8]. Due to the increasing interest of the scientific community in the characterization of tumor microenvironment, the present manuscript aims at offering a selection of recent literature illustrating novel approaches for the production and use of 3D cell cultures in the analysis of tumor interactions with ECM, blood vessels, mesenchymal cells and immune system

Models of 3D Cell Culture
Dissecting Tumor–Stroma Interactions in 3D Models
Interactions with
Interactions with Endothelial Cells
Interactions with Mesenchymal Cells
Interactions with Immune Cells
Conclusions
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