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. 2021 Mar 10;331:103–120. doi: 10.1016/j.jconrel.2020.12.057

Fig. 3.

Fig. 3

Human breast tumor-on-a-chip models. (a) Mimicking gradient generation on-chip. (Left) Microfluidic device for the study of breast cancer cell invasion into the 3D stroma. Bottom images show the spatial organization of cells encapsulated within a 3D matrix. (Right) Time-sequence for 4 days showing the invasion of EFG+ and EGF- SUM-159 breast cancer cells into the neighboring stroma. Reproduced with permission from [5] (Creative Commons Attribution 4.0 International License). (b) Mimicking fluid dynamics on chip. (Top) Tumor-mimetic microfluidic chip containing a realistic vascular network. (Bottom) Schematic representation of the vascular network, primary and secondary tumor chambers. Reproduced with permission from [105] (Creative Commons Attribution 4.0 International License). (c) Mimicking hypoxia effect on-chip. (A) Microfluidic chip showing the distribution of NHLF, HUVEC, and invasive GFP-MDA-MB-231 breast cancer cells. (B—C) Immunofluorescence image under normoxia (B) and hypoxia (C) conditions. (E-F) Quantification of the % of extravasated tumor MDA-MB-231 (E) and MCF7 (F) cells for all conditions. Reproduced with permission from [107] (Creative Commons Attribution 4.0 International License). (d) Mimicking tumor-stroma interactions on-chip. (A) The Ductal caricinoma in situ (DCIS) is embedded in a mammary duct consisting of the mammary epithelium and a basement membrane surrounded by stromal tissue (fibroblasts). (B) The microarchitecture of the DCIS and the surrounding tissue layers is reproduced in the breast cancer-on-a-chip microdevice comprised of the upper and lower cell culture chambers separated by an ECM-derived porous membrane. (C) cells are treated with paclitaxel from the basal side to simulate intravenous administration. (D) Paclitaxel treatment prevents growth of DCIS spheroids (white). (E) Fluorescence micrographs of DCIS spheroids at day 0 (left), day 3 without paclitaxel (middle), and 3 days with paclitaxel treatment (right). Reproduced with permission from [16] (Creative Commons Attribution 4.0 International License; CC BY 4.0).