Researchers from Rice University have developed a new model which may assist elucidate that how tumor manipulate vessels growth to receive benefits. This study was published in PNAS.
Angiogenesis, the formation of new blood vessels from existing ones, is a vital process during embryonic development, homeostasis, and tumor progression. This process starts when cells release angiogenic growth factors such as VEGF in response to hypoxia.
The selection of the tip and the stalk cell fate is critical for developing a functional vessel. This decision is mediated by Notch signaling pathway (2), an evolutionarily conserved cell–cell communication pathway involved in cell fate decisions in multiple contexts. This pathway is activated when Notch (transmembrane receptor) belonging to a particular cell interacts with Delta or Jagged (transmembrane ligands) belonging to its neighboring cell (trans-activation), thereby releasing the Notch intracellular domain (NICD).
Developing effective antiangiogenesis strategies remains clinically challenging. Unlike physiological angiogenesis, pathological angiogenesis comprises of many microvessels that do not fully mature or develop functionally, because the cell fate decision about which endothelial cells become the tip and lead the following stalk cells is dysregulated.
In this study, scientists devised a specific theoretical framework to decipher the cross-talk between two crucial players of the decision-making process of tip and stalk cell fate: VEGF and Notch-Delta-Jagged signaling. They find that high expression of Jagged, but not Delta, can destabilize the terminal differentiation into tip or stalk cells and give rise to a hybrid tip/stalk phenotype, a phenotype that can transform physiological into pathological angiogenesis.
Their results offer insights into why tumor-stroma communication often implicates Jagged.