Biomimetic strategies to recapitulate organ specific microenvironments for studying breast cancer metastasis

Abstract

The progression of breast cancer from the primary tumor setting to the metastatic setting is the critical event defining Stage IV disease, no longer considered curable. The microenvironment at specific organ sites is known to play a key role in influencing the ultimate fate of metastatic cells; yet microenvironmental mediated-molecular mechanisms underlying organ specific metastasis in breast cancer are not well understood. This review discusses biomimetic strategies employed to recapitulate metastatic organ microenvironments, particularly, bone, liver, lung and brain to elucidate the mechanisms dictating metastatic breast cancer cell homing and colonization. These biomimetic strategies include in vitro techniques such as biomaterial-based co-culturing techniques, microfluidics, organ-mimetic chips, bioreactor technologies, and decellularized matrices as well as cutting edge in vivo techniques to better understand the interactions between metastatic breast cancer cells and the stroma at the metastatic site. The advantages and disadvantages of these systems are discussed. In addition, how creation of biomimetic models will impact breast cancer metastasis research and their broad utility is explored.

The influence of matrix stiffness on the behavior of brain metastatic breast cancer cells in a biomimetic hyaluronic acid hydrogel platform

“…In this study, we utilized a biomimetic HA hydrogel platform to elucidate the mechanobiology associated with MDA‐MB‐231Br brain metastatic breast cancer cells. Currently, there are very few in vitro model systems to understand the mechanisms associated with breast cancer metastasis to the brain as compared to other metastatic sites such as bone, lungs, and liver . These model systems primarily consist of in vitro BBB models to study migration of breast cancer cells through the BBB and co‐cultures with live brain slices to understand the interaction of breast cancer cells with cellular components of the brain microenvironment .…”

“…Breast cancer commonly metastasizes to organs such as bones, lungs, liver, lymph nodes, and brain . Metastasis to distant organs marks the advanced stage of breast cancer no longer considered curable.…”

Emerging and Established Models of Bone Metastasis

“…Despite the push towards a focus on in vivo models by some, others believe that the ideal way to investigate the complex molecular mechanisms involved in this process is by advanced in vitro modeling [ 94 , 95 , 96 , 97 , 98 , 99 , 100 ]. These models consist of microfluidic models or advanced mathematical modeling, among others.…”

Human Organ-Specific 3D Cancer Models Produced by the Stromal Self-Assembly Method of Tissue Engineering for the Study of Solid Tumors

“…The heterogeneity and plasticity of stromal cells across the body indeed result in the formation of matrix microenvironments with distinct composition and organization, as illustrated in the papillar and reticular dermis of the skin [8]. These distinctive matrix microenvironments are likely to influence cancer behavior, development, and spreading [118,119], as shown with the variety of metastatic mechanisms described in pros-tate [120], colorectal [121], breast [122], bone [123,124], and skin [125] tissues. With the development of self-assembly approaches, it has become possible to recreate specific human matrix microenvironments in vitro.…”