Metastasis formation is the primary cause of cancer-related deaths. Preliminary data from our consortium identifies the perivascular niche as a hub of complex and dynamic cellular interactions and a source of microenvironmental secreted factors that promote primary tumor growth, early metastatic dissemination, and outgrowth at distant organs. We now aim to understand how the various stromal and immune cell types/states residing in this particular niche conspire to induce stemness and metastatic initiating competencies to cancer cells. To reach this goal, we will develop new microfluidicbased methodologies enabling an in-depth dissection of the physical networks of cellular and molecular interactions at the perivascular niche in space and time, early detection of metastatic dissemination in body fluids and high-throughput screening of molecules that intercept the metastatic process by targeting relevant cell-cell communication event(s) at the perivascular niche.