Vascular lumen formation

Abstract

The lumen of a blood vessel is essential for providing blood to any given tissue. Here, we discuss the molecular and cellular mechanisms underlying vascular lumen formation in invertebrates and vertebrates and highlight a new hypothesis describing oxygen transport in human malignant tumors. Several cellular mechanisms exist for blood vessel formation, that is vasculogenesis, intercellular and intracellular sprouting angiogenesis, and intussusceptive angiogenesis, all of which might follow common molecular principles to form a vascular lumen. The latter includes junctional remodeling and generation of apical endothelial cell surfaces, electrostatic deadhesion of these cell surfaces to create a small lumen between two or more apposing endothelial cells or a cavity within an endothelial cell, and force-dependent expansion or extension of the vascular lumen. Whereas these events require endothelial cells, vascular lumen formation in invertebrates mostly occurs in their absence. As therapeutically targeting endothelial cells alone does not prevent vascular supply and growth of human malignant tumors, the possibility exists that some tumors employ invertebrate-like mechanisms of vascular lumen formation. Whereas the molecular mechanisms of endothelial cell-based vascular lumen formation are beginning to be understood, it is still largely unknown how invertebrates and some malignant tumors establish a circulatory system in the absence of endothelium.