Author:
Madeo Marianna,Colbert Paul L.,Vermeer Daniel W.,Lucido Christopher T.,Vichaya Elisabeth G.,Grossberg Aaron J.,Cain Jacob T.,Muirhead DesiRae,Rickel Alex P.,Hong Zhongkui,Spanos William C.,Lee John H.,Dantzer Robert,Vermeer Paola D.
Abstract
AbstractPatients with densely innervated tumors do worse than those with less innervated cancers. We hypothesize that neural elements are acquired by a tumor-induced process, called neo-neurogenesis. Here, we use PC12 cells in a simple system to test this hypothesis. PC12 cells extend processes, called neurites, only when appropriately stimulated. Using this system, we show that patient tumors release vesicles (exosomes) which induce PC12 neurite outgrowth. Using a cancer mouse model, we show that tumor cells compromised in exosome release grow slower and are less innervated than controls indicating a contribution of innervation to disease progression. We find that neo-neurogenesis is mediated in part by the axonal guidance molecule, EphrinB1, contained in exosomes. These findings support testing EphrinB1 blockers to inhibit tumor innervation and improve survival.One Sentence SummaryTumors release exosomes which not only promote their own innervation but also potentiate their growth.
Publisher
Cold Spring Harbor Laboratory