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

Abstract

Most 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.

Tumor microenvironment complexity and therapeutic implications at a glance

“…In order to develop a reliable tool for personalized cancer therapy and drug development, it is essential to preserve the key characteristics of the original tumor. Recent advances on three dimensional (3D) platforms through the use of labon-chip and microfluidic devices [17] have provided an enormous opportunity to better stimulate the function and biology of TME and to bridge the translational gap between preclinical and clinical settings [18].…”

P2X7R promotes angiogenesis and tumour‐associated macrophage recruitment by regulating the NF‐κB signalling pathway in colorectal cancer cells

“…Tumour cells were implanted to construct a murine model that showed that the higher levels of P2X7R caused changes in the tumour stroma via TAM recruitment and angiogenesis, as well as increased CSC features. The tumour microenvironment is critical in the process of metastasis 41 . As previously study, metastasis involves M2 but not M1 macrophages that support tumour formation 42 .…”

Microfluidic modelling of the tumor microenvironment for anti-cancer drug development

“…Most current reviews either focus on specific fields such as cell migration and 3D cell culture or highlight the biological applications of in vitro tumor models [14][15][16], with limited emphasis on their contribution to anti-cancer drug screening and development. This review aims to provide readers with a detailed discussion on the current state-of-art microfluidics-based tumor models, with a special focus on their application in anti-cancer drug screening and the engineering approaches to recapitulate the tumor microenvironment ( Figure 1).…”