Biomimetic Microfluidic Platforms for the Assessment of Breast Cancer Metastasis

Abstract

Of around half a million women dying of breast cancer each year, more than 90% die due to metastasis. Models necessary to understand the metastatic process, particularly breast cancer cell extravasation and colonization, are currently limited and urgently needed to develop therapeutic interventions necessary to prevent breast cancer metastasis. Microfluidic approaches aim to reconstitute functional units of organs that cannot be modeled easily in traditional cell culture or animal studies by reproducing vascular networks and parenchyma on a chip in a three-dimensional, physiologically relevant in vitro system. In recent years, microfluidics models utilizing innovative biomaterials and micro-engineering technologies have shown great potential in our effort of mechanistic understanding of the breast cancer metastasis cascade by providing 3D constructs that can mimic in vivo cellular microenvironment and the ability to visualize and monitor cellular interactions in real-time. In this review, we will provide readers with a detailed discussion on the application of the most up-to-date, state-of-the-art microfluidics-based breast cancer models, with a special focus on their application in the engineering approaches to recapitulate the metastasis process, including invasion, intravasation, extravasation, breast cancer metastasis organotropism, and metastasis niche formation.

ARHGEF19 promotes the growth of breast cancer in vitro and in vivo by the MAPK pathway

“…Breast cancer is known as the most common malignancy in women [4]. Early breast cancer is curable, but patients with early breast cancer have no symptoms [17].…”

“…However, metastasis remains the leading cause of breast cancer-related death [3]. Due to the high metastatic nature of advanced breast cancer, current treatments have little effect [4,5]. Targeted therapy of breast cancer has made a series of outstanding achievements, many targeted therapy drugs are used in clinical practice and clinical trials [6,7].…”

Microfluidics meets 3D cancer cell migration

“…This property is relevant for cell migratory behavior in a 3D matrix environment compared with cells that prefer directional migration on 2D stiffer substrates. Traditional 3D in vitro models, such as Boyden Chambers, and heterogeneous tumor spheroid invasion assays compared with in vivo models are inexpensive, require less expertise to operate, and can better recapitulate cell-cell/ cell-ECM interaction when embedded in hydrogel matrices [35]. Cell migration behavior observed using 3D cell culture and 2D microfluidic models have provided insights into more guided cell trajectory in response to a biochemical signal or to analyze cellular response by mimicking vascular networks using micro-confinement geometries [36,37].…”

Application of Microfluidic Systems for Breast Cancer Research

“…Extravasation is the process by which CTCs exit the circulatory system to settle in a new organ system; breast CTCs have been found to primarily extravasate into four organs, the bone, brain, liver, and lungs, where they then form secondary tumors that may be fatal [13,14]. Breast cancer metastasis is under intense investigation, and a comprehensive review of biomimetic microfluidic platforms developed for its assessment has recently been presented [15]. However, in addition to investigating the mechanisms of metastasis, microfluidic devices are also useful tools in exploring new breast cancer detection and treatment methods, with microfluidic devices having been used to test and troubleshoot various treatment modalities for development of new therapeutic strategies [16,17].…”