Cancer metastases represent the greatest challenge of modern medicine due to their high impact on patient mortality. Our lab studies the metastatic process through 2D and 3D human in vitro models across multiple scales. We successfully design and develop human vascularized macro and microfluidic systems that mimic in vivo biophysical and biochemical organ specific microenvironment with the aim to study different steps of metastasis. Particularly, we are able to analyze the crosstalk between breast cancer and endothelial cells in organ specific microenvironments through the establishment of endothelial monolayers or perfusable microvascular networks. We study the gene silencing effect in each step of extravasation, which can be dissected in adhesion, trans-endothelial migration and early invasion of secondary organs leading to metastatic colonization.