TABLE 1.
Summary of microfluidic devices used in studies of breast cancer metastasis.
| References | Cells used | Device properties | Metastatic niche | Remarks |
| Yankaskas et al., 2019 | MDA-MB-231 and Patient-Derived Xenografts (PDX) | -Microfluidic Assay for the quantification of Invasion -Comprised of parallel Y shaped microchannels | Invasion | -Comparison showed migratory cells correlated with their metastatic potential -Device has the potential to be developed into metastatic prediction assay. |
| Gioiella et al., 2016 | Epithelial Breast Cancer Cells (MCF7), stroma (fibroblast- assembled ECM) | -PDMS based device with barrier region in between cells -Co-culture of MCF7 and stroma in a single device | Invasion | -Higher degree of similarity observed when compared to in vivo models. |
| Blaha et al., 2017 | MDA-MB-231 and Human Umbilical Vein Endothelial cells (HUVECs) | Microfluidic chamber having 3D collagen matrix constructs -Co-culture of MDA-MB-231 and HUVEC in the collagen matrix | Invasion | -Cancer cell invasion significantly increased in the presence of HUVEC cells |
| Truong et al., 2019 | Breast cancer (SUM-159) and Cancer Associated Fibroblasts (CAFs) | -Microfluidic 3D organotypic model -PDMS based device for co-culture of cells to recapitulate the breast tumor microenvironment | Invasion | -Helped cancer-stroma communication -Increased cancer cell migration speed -Transcriptome analysis revealed novel molecular targets associated with breast cancer invasion |
| Cui et al., 2017 | Primary human vascular endothelial cells and MDA-MB-231 cells | -Microfluidic device developed using photolithography of SU-8 photoresist -Consisted two flow layers along with a central porous membrane (4 mm*4 mm) -Bottom layer consisted of multiple microchamber for cell collecting | Intravasation | -Quantified transendothelial migration of breast cancer cells under different stress levels, i.e., 2.5 dyne/cm2 and 10 dyne/cm2 -More breast cancer cells migrated through the endothelial layer for low shear stress as compared to the high-stress level |
| Nagaraju et al., 2018 | HUVECs, MDA-MB-231, and MCF7 | -Microfluidic device consisting of three layers: inner layer for tumor cells, central for stroma, and outer layer for vasculature as well as surrounding media channels -Tumor and stroma layer consisted of collagen as a major protein whereas fibrin was selected for the vascular layer | Intravasation | -Higher number of cancer cells invaded the stromal region in presence of endothelial vascular networks -Different morphologies were observed for cancer cells in the presence or absence of endothelial cells in the vascular network -Presence of cancer cells make endothelial networks to be leakier and more permeable - Endothelial cells are a key source for leading the intravasation process |
| Shirure et al., 2018 | Normal human lung fibroblasts (NHLFs), Endothelial colony-forming cell-derived endothelial cells (ECFC-ECs), MDA-MB-231, MCF-7, and colorectal cancer cell line (Caco-2) | -Consisted of three distinct tissue layers parallel to each other -Communication between the layers is via microporous walls -Central layer was for vascular networks while side layers for cells loading | Intravasation | -The designed device was able to biologically mimic a relevant tumor microenvironment between the arterial end of capillary and tumor -Device can culture wide variety of cancer cell -Primary tumor organoids prepared were workable for several weeks |
| Chen M. B. et al., 2016 | HUVEC (Human Umbilical Vein Endothelial Cells), NHLF (Normal human lung fibroblasts), MDA-MB-231, A-375 MA2, and 4T1 cells | -Microfluidic based device with microvascular networks and three independent hydrogel regions separated by media channels in between. -HUVECs (human umbilical vein endothelial cells) and NHLFs (Normal human lung fibroblasts) were used for creating vascular networks | Extravasation | -B1 integrin expression was an important aspect for transendothelial migration of breast cancer cells along with stabilizing protrusions and contacting the basement membrane -Further studies are needed to learn more about the role of B1 integrin. |
| Chen et al., 2017 | HUVECs and NHLFs | -PDMS based device for microvasculature extravasation examine | Extravasation | -Tumor cells extravasation from smaller vessels showed greater physiological relevance than traditional models -All processes like tumor cells interacting and invading endothelial basement membrane tracked via immunofluorescent techniques |
| Song et al., 2018 | HUVECs, NHLF MCF-10A, MCF-7, and MDA-MB-231 | -Device fabricated using PDMS (polydimethylsiloxane) using standard photolithography -Device consisted of a central gel layer and two media channels | Extravasation | -Cells were exposed to two different conditions, i.e., hypoxia and normoxic state -HIFs: markers for hypoxia -Knockdown of HIF-1α in hypoxic tumor decreased the extravasation rate of all cancer cells lined tested |
| Boussommier-Calleja et al., 2019 | Cytoplasm-labeled GFP-endothelial cells (HUVECs), NHLF, Monocytes, MDA-MB-231, and MDA-MB-435 | -PDMS based microfluidic device composed of five channels connecting two cell media reservoirs compartment -Central compartment filled with a cell-hydrogel mixture | Extravasation | -Monocytes affects cancer cell extravasation and has a key role in the metastatic process -Replicated phenomena seen in vivo as well as the discovered undefined role of monocytes in the tumor microenvironment -This device promises a powerful model for anti-cancer drug therapy in future |
| Bersini et al., 2014 | Bone marrow-derived human mesenchymal stem cells (hBM-MSCs), Red fluorescent protein (RFP)-HUVECs, MDA-MB-231 | -Microfluidic device consisted of three media channels and four independent channels for gel -Device fabricated using PDMS -8 gel regions having to interface with central media channel were adopted for cell interactions study | Breast cancer bone metastasis | -CXCR2 and CXCL5 are the major events resulting in extravasation and the migration rate of cancer cells -Inhibition of those agents can serve as anti-cancer drug therapy and shows the therapeutic potential |
| Jeon et al., 2015 | hBM-MSCs, GFP-HUVECs, osteo-differentiated hBM-MSCs, MCF-10A, MDA-MB-231 | -PDMS based device with central hydrogel compartment along with lateral media channels -Cover glass bonded to PDMS and ports created by biopsy punches | Bone Metastasis and Extravasation | -Cancer cell extravasation rates significantly higher in the bone microenvironment -A3 adenosine receptor showed potential in the prevention of breast cancer bone extravasation -Presence of flow condition showed a favorable environment for cancer cell migration into the surrounding matrix |
| Mei et al., 2019 | MLO-Y4 cells, RAW264.7 cell line, HUVECs, MDA-MB-231 | -Microfluidic device consisting of osteocyte channel, lumen channel, and side channels fabricated using PDMS -Microfluidic chip were arrayed for increasing throughput | Breast cancer bone metastasis | -Oscillatory fluid flow was induced that was relevant to the physiological model -Flow condition reduced the number of extravasated cells as well as the distance traveled by them when compared to non-flow conditions |
| Kong et al., 2016 | HUVECs, MDA-MB-231, MCF-7, and ACC-M | -Device consisted of four layers: one glass substrate layer, two PDMS membrane, and one porous membrane -Porous membrane in between PDMS layers -four parallel and branched microchannels for creating vasculature on top of PDMS layers. | Breast cancer lung metastasis | -MDA-MB-231 showed greater lung metastasis potential among all cancer cell lines tested in the microfluidic model developed -When compared with the animal model, the microfluidic model showed physiological similarity |
| Kim et al., 2020 | Liver epithelial THLE-2 cells, Primary liver fibroblasts (LFs), Human liver sinusoidal endothelial cells (LSECs), liver hepatocytes, MCF-7, MDA cell lines, and MCF-10A | -Platform consisted of the top layer, bottom layer, and middle layer -Middle layer made of thin porous PDMS membrane interfaced with top and bottom layers | Breast cancer liver metastasis | -This device enabled the recapitulation of the human liver microenvironment consisting of distinct types of liver cells -Breast cancer cell adhesion increased by breast cancer-derived extracellular vesicles EVs in the liver niche |
| Tian et al., 2020 | HUVECs, MCF-7, MDA-MB-231 | -Device consisted of two tissue chambers and two media channels -Media channels joined to inlet and outlet on each end -Porous membrane in between two PDMS layers | Breast cancer liver metastasis | -Precision cut tissue slices (PTS)-based liver–kidney on a chip model was developed |
| Xu et al., 2016 | Astrocytes, primary rat BMECs, A549, MDA-MB-231, M624, and BEL-7402 | -Device had 16 independent units connected by a microchannel network -Each unit had four uniforms BBB (Blood Brain Barrier) regions and shared the same outlet in the middle of the chip | Blood-brain barrier model and extravasation | -Developed device effectively replicated BBB in normal and diseased conditions -Astrocytes in BBB plays a vital role in interactions between endothelial cells and cancer cells -Results were consistent with other in vivo and in vitro studies |
| Oliver et al., 2019 | Astrocytes, HCMEC/D3 endothelial cells cancer cells, MCF-10A, MDA-MB-231, MDA-MB-231-BR, and brain seeking subclone of MDA-MB-231 | -Machine learning algorithms trained for prediction of metastatic potential of breast cancer cells across BBB regions -Microfluidic device composed of two chambers separated by a porous membrane -Fabricated using PDMS | Extravasation of cancer cells into brain metastatic niche | -Neural networks, Adaboost and Random forest showed the best results -MDA-MB-231-BR showed significant extravasation compared to other cells -Future studies involving fluid flow and the addition of cells would help better recapitulation of BBB in vitro. |