Metastasis on-a-chip platform to follow in real-time the extravasation process and collect extravasated cancer cells
Résumé
Metastasis is the main cause of mortality in patients with solid tumors. Indeed, some malignant cancers acquire the ability to spread through the organism and form metastasis in targeted organs. Among several key steps, extravasation of cancer cells across the endothelium, which features the exit of cancer cells from blood circulation into tissues, is necessary for the cells to reach their niche. The molecular mechanisms underlying the extravasation process of cancer cells are not yet fully understood, and the specific phenotype of extravasated cells remains unclear. Many microfluidic devices have been developed with the aim to understand the extravasation steps, but few of them allowed a convenient way to collect extravasated cancer cells. We present an original biomimetic microfluidic device with a specific design that allows to study and follow cancer cell extravasation across a reconstituted endothelium in real-time using live imaging. Metastatic human breast adenocarcinoma cells (MDA-MB-231) wereinjected inside the upper channel of the device under flow conditions and our preliminary results revealed that a population of the cancer cells remained attached to the endothelium and some of them were able to extravasate. A transcriptomic analysis was performed on collected extravasated cells and these cells were found to express high levels of CD44 and Erb2 and low levels of KDR and CDH5. This profile matched that of MDA-MB-231 cells and not that of endothelial cells and confirmed that circulating cancer cells had actually crossed the microdevice endothelium. Our device will enable to understand the flow effects that occur inside a complex microfluidic channel network and to collect extravasated cancer cells. Collecting this rare population of disseminated cells for further molecular and biological analyses in order to find new therapeutic strategies is a challenging goal
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