Radiation-induced modifications of the tumor microenvironment promote metastasis

摘要: Radiotherapy is successfully used to treat cancer. Emerging evidence, however, indicates that recurrences after radiotherapy are associated with increased local invasion, metastatic spreading and poor prognosis. Radiation-induced modifications of the tumor microenvironment have been proposed contribute aggressive behavior, an effect also referred as bed effect, but putative mechanisms involved remained largely elusive. We recently demonstrated irradiation prospective stroma impairs de novo angiogenesis through sustained inhibition proliferation, migration sprouting endothelial cells. Experimental tumors growing within a pre-irradiated field reduced growth, hypoxia, necrosis, invasion distant metastasis. Mechanisms progression involve adaptation cells hypoxic conditions well selection invasive capacities. The matricellular protein CYR61 integrin αVβ5 emerged molecules cooperate mediate lung Cilengitide, small molecular inhibitor αV integrins prevented metastasis formation. These results represent conceptual advance understanding indicate might be potential therapeutic approach for preventing in patients at risk post-radiation recurrences.