Preclinical animal models such as patient-derived xenograft (PDX) mouse models have been established to study cancer stemness and stroma-tumor interactions, predict potential biomarkers, and identify anti-cancer therapeutic strategies ( 5). Therefore, it is important to explore how the interactions between CTCs and the microenvironment in the secondary organ affect cancer cell extravasation. In the secondary organ, factors including the pre-metastatic microenvironment (e.g., resident stromal cells) determines the extravasation sites and plays an important role in metastasis progression ( 4). Surviving CTCs can then adhere to the endothelium and extravasate into the distant secondary organ and subsequently progress into metastatic tumors ( Figure 1). Then, these tumor cells invade surrounding tissues, intravasate to the nearby microvasculature as either single cells or cell clusters, and become circulating tumor cells (CTCs), often aggregating with platelets or monocytes, enabling them to withstand fluid shear stress or anoikis ( 3) and avoid attack by circulating NK cells. Cancer metastasis often begins when tumor cells undergo an epithelial-to-mesenchymal transition (EMT), in which they acquire higher motility and invasiveness and break away from the primary tumor ( 2). In this mini-review, we highlight recent microfluidic vascular models of tumor cell extravasation and explore how this approach contributes to development of in vitro disease models to enhance understanding of metastasis in vivo.ĭespite advances in cancer treatment such as surgical resection and adjuvant therapy, cancer metastasis still accounts for more than 90% of cancer patients’ deaths ( 1). To date, extensive efforts have been made to capture key features of the microvasculature to reconstitute the pre-metastatic niche and investigate dynamic extravasation behaviors using microfluidic systems. These in vitro technologies recapitulate key aspects of metastatic cancer, including the process of tumor cell arrest and extravasation at the site of the metastatic tumor. 2Biomicrofluidics Lab, Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South KoreaĮmerging microfluidic disease models have amply demonstrated their value in many fields of cancer research.1Mechanobiology Lab, Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States.Seunggyu Kim 1,2†, Zhengpeng Wan 1†, Jessie S.
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