Role of the Hypoxic-Secretome in Seed and Soil Metastatic Preparation.

During tumor growth, the delivery of oxygen to cells is impaired due to aberrant or absent vasculature. This causes an adaptative response that activates the expression of genes that control several essential processes, such as glycolysis, neovascularization, immune suppression, and the cancer stemness phenotype, leading to increased metastasis and resistance to therapy. Hypoxic tumor cells also respond to an altered hypoxic microenvironment by secreting vesicles, factors, cytokines and nucleic acids that modify not only the immediate microenvironment but also organs at distant sites, allowing or facilitating the attachment and growth of tumor cells and contributing to metastasis.