TABLE 1.
The bio-medical relevance of breast cancer-on-chip (BCoC) systems.
| Chip role | Chip design | Chip relevance | References |
|---|---|---|---|
| simulation of BC cell migration and invasion across the basement membrane | 3D microfluidic with MX1 BC cells for migration model | amoeboid- and mesenchymal-like motility and collective pattern of migration | Toh et al. (2018) |
| investigation of interstitial fluid pressure on the EMT | MDA-MB-231 BC cells embedded within a gel of type I collagen | high pressure increases BC cell collective invasion via EMT biomarkers (SNAIL, VIM, CDH1) | Piotrowski-Daspit et al. (2016) |
| early-stage BC modeling | MCF10-DCIS spheroids co-cultured with human mammary ductal epithelial cells and mammary fibroblasts embedded in a 3D ECM | assessment of efficacy and toxicity of paclitaxel | Choi et al. (2015) |
| investigation of BC-immune cell interactions to assess T-cell recruitment and role of TME on cytotoxic T-cell recruitment | CCs (MCF7, MDA-MB-231), monocytes (THP-1), ECs (HUVECs), T-cells (TALL-104) | hypoxic environment in spheroid culture recruited more T-cells compared with dispersed CCs; the presence of monocytes synergistically increased T-cell recruitment at the tumor site | Aung et al. (2020) |
| role of TAMs in BC invasion | 3D microfluidic tumor-macrophage system with MDA-MB-231 TNBC cells | BC cells promote the differentiation of human monocyte U937 cells into TAMs | Mi et al. (2019) |
| role of breast fibroblasts and ECM components in modulation of BC cell migration | 3D microfluidic model of TME including MDA-MB-231 TNBC cells | in the presence of normal human fibroblasts, a fibronectin-rich collagen matrix increases metastatic MDA-MB-231 TNBC cells migration due to an overexpression of MMPs | Lugo-Cintrón et al. (2020) |
| role of hybrid BC-mesenchymal stem/stromal cells to enhance chemoresistance and metastasis | cell engulfment-on-chip: MDA-MB-231 TNBC cell line and MSCs | primary BC and metastases contain hybrid BC cell population that express EMT biomarkers (ZEB1 and SMA) due to MSC engulfment in BC cells that stimulates metastasis | Augimeri et al. (2023), Chen et al. (2019) |
| evaluation of intercellular communication between BC cells and adipose-derived stromal/stem cells (ASCs) | microfluidic device co-culturing MDA-MB-231 cells and ASCs | tumor cells exhibit enhanced growth, a more aggressive phenotype, polarization toward ASCs, and an increased resistance to paclitaxel | Rahman et al. (2020) |
| replication of ECM activation during BC progression | tumor/inner chamber (MCF7); stromal/external chamber (3D tissue micro-modules formed by NFs or/and CAFs-assembled ECM) | MMPs overexpression in activated tissues; overexpression of fibronectin and hyaluronic acid, as well as collagen reorganization in the ECM during tumor progression | Gioiella et al. (2016) |
| evaluation of NPs/carbon dots-based drug delivery system | microvessel wall, ECM, BT549 (TNBC), T47D (non-TNBC) tumor spheroids, carbon dots functionalized with polyethylene glycol, acid folic, and doxorubicin | evaluation of dynamic transport behaviour and in situ cytotoxicity; rapid drug screening in pre-clinical studies | Chen et al. (2018) |
| multi-drug resistance assay | microfluidic single-cell technique | study of drug efflux inhibition on a single MDA-MB-231 TNBC cell | Parekh et al. (2019) |
| BC-on-chip | MDA-MB-231 TNBC cells aggregates embedded in a dextran-based hydrogel, CAR-T cell perfusion, and endothelial barrier | model for CAR-T cell infusion, recruitment, and infiltration into solid tumors for monitoring of dynamic cytokine release over more than 1 week | Maulana et al. (2024) |
Abbreviations: ASCs, adipose-derived/stromal/stem cells; BC, breast cancer; CAFs, cancer associated fibroblasts; CAR-T, cells–chimeric antigen receptor-T, cell; CCs, cancer cells; CDH1 – E-cadherin gene; CDs, carbon dots; DCIS, ductal carcinoma in situ; ECM-extracellular microenvironment; ECs, endothelial cells; EMT, epithelial-mesenchymal transition; MMPs, matrix metalloproteinases; MSCs, mesenchymal stem/stromal cells; NFs, normal fibroblasts; NPs, nanoparticles; SMA, smooth muscle actin; VIM, vimentin; TAMs, tumor-associated macrophages; TME, tumor microenvironment; TNBC, triple negative breast cancer.