Epithelial-mesenchymal interactions are linked to neovascularization.

Lung morphogenesis is dependent on interactions between mesenchymal and epithelial cells. We have previously demonstrated that inhibition of neovascularization by endothelial monocyte-activating polypeptide (EMAP) II also attenuates fetal lung morphogenesis in vivo, and hypothesized that epithelial-mesenchymal interactions are regulated by vascular signals. To address this postulate, we evaluated the formation of epithelial cysts in vitro and assessed this complex interaction through: (i) identification of vascular formation in vitro; (ii) assessment of the effect of selective vascular inhibition on cell viability, proliferation, and cellular interactions as measured by epithelial cyst formation; and (iii) examination of whether there is an interdependent relationship between epithelial and mesenchymal cells and a vascular mediator's protein expression. Vascular networks in vitro formed in direct relationship to the presence of epithelial cysts. Disruption of the vasculature by delivery of a selective antiangiogenic protein EMAP II was associated with disruption of epithelial cyst formation. Lastly, control of the vascular formation regulatory protein EMAP II is a direct result of epithelial-mesenchymal cell interactions. These findings suggest that vascular formation modulates and is modulated by the normal cellular communication and interactions that direct lung morphology.