Hyperthermia Inhibits Angiogenesis by a Plasminogen Activator Inhibitor 1-dependent Mechanism

摘要: Hyperthermia (HT) associated with radiotherapy or chemotherapy is a promising method for cancer treatment, although the molecular mechanisms of this process are not well understood. HT exhibits various antitumor effects, including damage tumor vasculature. Here, we investigate effect on in vitro and vivo angiogenesis. We show that heat treatment endothelial cells (ECs) affect their differentiation into capillary-like structures two models Furthermore, formation new vessels promoted by angiogenic inducers chick embryo chorioallantoic membrane assay impaired after treatment. These effects cannot be explained direct cytotoxicity but dependent modulation angiogenesis-involved genes. Gene expression profile ECs subjected to shock demonstrates plasminogen activator inhibitor 1 (PAI-1), protein involved control extracellular matrix degradation, specifically up-regulated. The use anti-PAI-1-neutralizing antibodies reverts EC morphogenesis vessel formation. Moreover, microvessel outgrowth from PAI-1 −/− aortic rings was affected compared +/+ mice. Heat murine mammary adenocarcinomas results inhibition growth, reduction number an increase expression. indicate heat-mediated induction important pathway which exerts its activity may represent rationale combined therapy based antiangiogenic molecules.