Tumor-derived exosomes and their local and systemic effects. Exosomes alter the tumor microenvironment (TME) and prepare distant tissue sites for metastasis. In the TME, exosomes interact with all cellular components and impact on the stromal, immune as well as vascular compartments. They access tumor-draining lymph nodes, facilitating entry of metastatic cells. They also carry and transfer oncogenes and oncogenic proteins to metastasizing tumor cells. Systemic effects of exosomes at distant tumor sites require that exosomes migrate via the blood or lymph. Once in place, they prepare tissue sites for metastasis or alter/educate the bone marrow (BM) environment, creating a pre-metastatic niche to promote tumor invasion and growth. They re-program mesenchymal stem cells (MSC) as well as progenitor hematopoietic cells. Tumor-derived exosomes interact with vascular endothelial cells (EC) favoring their proliferation, sprouting and the angiotube formation.