Metastasis in context: modeling the tumor microenvironment with cancer-on-a-chip approaches.

Jelle J. F. Sleeboom,Hossein Eslami Amirabadi,Jaap M. J. den Toonder,Cecilia M. Sahlgren,Poornima Nair

doi:10.1242/dmm.033100

Abstract

ABSTRACTMost cancer deaths are not caused by the primary tumor, but by secondary tumors formed through metastasis, a complex and poorly understood process. Cues from the tumor microenvironment, such as the biochemical composition, cellular population, extracellular matrix, and tissue (fluid) mechanics, have been indicated to play a pivotal role in the onset of metastasis. Dissecting the role of these cues from the tumor microenvironment in a controlled manner is challenging, but essential to understanding metastasis. Recently, cancer-on-a-chip models have emerged as a tool to study the tumor microenvironment and its role in metastasis. These models are based on microfluidic chips and contain small chambers for cell culture, enabling control over local gradients, fluid flow, tissue mechanics, and composition of the local environment. Here, we review the recent contributions of cancer-on-a-chip models to our understanding of the role of the tumor microenvironment in the onset of metastasis, and provide an outlook for future applications of this emerging technology.

Highlights

Researchers studying cancer have been focusing mainly on the genetic origin of the disease, which has led to major advances in cancer detection and treatment
We have highlighted how different cues from the tumor microenvironment (TME) can affect the onset of metastasis, and we have reviewed the most recent cancer-on-a-chip models (CoC) developments showing how these models can help decipher the complex interplay within and between the cancer cells and the TME
In a much broader perspective, the technologies developed for CoC models are not limited to studying cancer invasion and the TME alone

Summary

Introduction

Researchers studying cancer have been focusing mainly on the genetic origin of the disease, which has led to major advances in cancer detection and treatment. Cellular components of the tumor microenvironment This section highlights the most studied cells in the TME: inflammatory cells, cancer-associated fibroblasts (CAFs; Box 1), and endothelial cells (ECs; Fig. 1C). The compartments can be used to reproducibly create a niche in which ‘mini-tumors’ can grow, develop and interact within their own specified microenvironment, to human tumors (reviewed in Lee et al, 2016; Portillo-Lara and Annabi, 2016) Their small size allows the cellular and matrix composition, local biochemical gradients and mechanical forces, such as shear and stretch, to be highly controlled. Different cues from the TME can be modeled and accurately controlled in these chips These properties make CoC devices an excellent tool for studying the interactions between cancer cells and their microenvironment.

G Lumen chip H Compartmentalized chip I Y chip

Conclusion