AKR1B10 (Aldo-keto reductase family 1 B10) promotes brain metastasis of lung cancer cells in a multi-organ microfluidic chip model

Advanced Microfluidic Models of Cancer and Immune Cell Extravasation: A Systematic Review of the Literature

“…A shear stress of 0.25 dyn/cm 2 applied in a microvascular network decreased the endothelial permeability compared to static conditions, possibly due to the tightening of endothelial cell junctions (Jeon et al, 2015). In line with this result, 10-fold lower shear stress values applied on an endothelial monolayer were sufficient to induce the expression of VEcadherin and ZO-1, both involved in the formation of endothelial cell junctions (Liu et al, 2019). However, a minimal shear stress threshold to induce modifications in endothelial cell behavior seems to exist, since VE-cadherin and ICAM-1, an adhesion molecule involved in leukocyte-endothelial cells interactions, were not upregulated by a 100-fold lower value of shear stress (Sharifi et al, 2019).…”

“…The presence of brain specific cells combined with flow stimulation increased the tightness of brain-specific microvessels forming the blood-brain barrier by decreasing the endothelial permeability if compared to conditions without astrocytes and shear stimulus. These results indicate that astrocytes modify the endothelium properties and that this might change the cancer cell extravasation outcomes, approaching a condition more similar to the in vivo situation (Liu et al, 2019).…”

“…In this context, beyond the presence of tissue-specific cells in the model, the presence of a tissue-specific endothelium would allow the study of cancer cell and leukocyte extravasation with a higher reliability, since the phenotypic traits of the endothelium strongly depends on its anatomical origin (Marcu et al, 2018). One of the studies analyzed in this review introduced a brainspecific endothelium mimicking the blood-brain barrier (Liu et al, 2019). However, the results on extravasation were not compared with those obtained with a non-specific endothelium, which did not allow a direct confirmation of the effects of a tissue-specific endothelium on extravasation.…”

“…Besides investigating the effects of cell deformation, microfluidic models were exploited to distinguish the extravasation ability of cancer cells with a different degree of malignancy (Chen et al, 2013) as well as of cancer cells originating from different primary tumors (Tourovskaia et al, 2014). For instance, the presence of hyaluronan in the pericellular matrix of breast cancer cells (Brett et al, 2018) or the expression of specific proteins implicated in brain cancer development (Liu et al, 2019) were studied in relation to the metastatic potential of cancer cells, demonstrating that microfluidic extravasation models are able to capture differences in cell malignancy and allow identifying some of the elements responsible of a high metastatic potential. Breast cancer cells with different metastatic potential were also pre-conditioned in hypoxic conditions before injection in a microfluidic device, demonstrating that hypoxic cells have a higher extravasation rate compared to normoxic cells (Song et al, 2018).…”

“…The negative influence of cancer cells in the maintenance of an intact endothelium was observed through fluorescence microscopy imaging. Immunofluorescence analysis allowed to obtain information about the endothelium integrity through the visualization of two tight junction proteins, ZO-1 and VE-cadherin, expressed by endothelial cells, both showing a decreased expression during cancer cell extravasation (Liu et al, 2019). The mechanisms that leads to endothelium disruption by cancer cells have not yet been clarified and can either depend on a local damage of the endothelium by cell contact or on the secretion of factors affecting the endothelial cell junctions.…”