Glioblastoma: a pathogenic crosstalk between tumor cells and pericytes.

摘要: Cancers likely originate in progenitor zones containing stem cells and perivascular stromal cells. Much evidence suggests play a central role tumor initiation progression. Brain (pericytes) are contractile function normally to regulate vessel tone morphology, have cell properties, interconvertible with macrophages involved new formation during angiogenesis. Nevertheless, how pericytes contribute brain infiltration is not known. In this study we investigated the underlying mechanism by which most lethal cancer, Glioblastoma Multiforme (GBM) interacts pre-existing blood vessels (co-option) promote Here, using mouse xenografts laminin-coated silicone substrates, show that GBM malignancy proceeds via specific previously unknown interactions of pericytes. Two-photon confocal live imaging revealed employ novel, Cdc42-dependent actin-based cytoplasmic extensions, call flectopodia, modify normal activity This results co-option modified support expansion margin. Furthermore, our data provide for cell/pericyte fusion-hybrids, some located on abnormally constricted ahead linked tumor-promoting hypoxia. Remarkably, inhibiting Cdc42 impairs converts phagocytic/macrophage-like phenotype, thus favoring an innate immune response against tumor. Our work, therefore, identifies first time key contact-dependent interaction switches pericyte from tumor-suppressor tumor-promoter, indicating may harbor seeds its own destruction. These development therapeutic strategies directed (preventing incorporation modification vessels), possibly combination anti-angiogenesis (blocking formation), could lead improved vascular targeting only but also other cancers.