Abstract

IntroductionBreast cancer is one of the most malignant cancer types which is the second leading cause of cancer-associated deaths in women. Breast cancer begins as a local disease which can then metastasize to lymph nodes and distant sites. The metastasis of breast cancer is mainly to bone, lung and liver. Being the leading cause of cancer related deaths, it is essential to understand the complex metastasis phenomenon to develop new diagnostic and therapeutic strategies. In this study, we aim to develop a lab-on-a-chip (LOC) system to detect the metastatic capacities of breast cancer cells to different target tissues.Material and methodsThe triple negative breast cancer cell line MDA-MB-231 was selected based on its high metastatic capacity, while normal lung, liver and bone fibroblasts WI-38, BRL3A and HS-5 and human umbilical vein endothelial cell line HUVEC-C were used to generate target tissue microenvironments and endothelial monolayer, respectively. A three-channel LOC system, one for endothelial monolayer formation, one for mimicking target tissue microenvironment and one for media supply, was used. The seeding cell densities, common medium composition and ECM components for microenvironment were optimised for the LOC system. Following addition of cancer cell lines to the endothelial monolayer channel, invasion and extravasation capacities to different target sites were determined by tracking 3D distribution of fluorescently labelled cancer cells up to four days.Results and discussionsMDA-MB-231 cells were shown to invade and extravasate preferentially to lung and liver microenvironments, while their movement to bone or cell-free target sites was limited. The observed results were in agreement with the previously reported phenotype of MDA-MB-231 cell lines.ConclusionOur results show that tissue- specific cell lines in a LOC system can be used to mimic target tissue microenvironments and evaluate different invasion and extravasation capacities of breast cancer cell lines to different target sites.

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