Notch signaling regulates vessel structure and function via Hspg2.

Area of Science:

• Vascular Biology
• Molecular Signaling
• Oncology

Background:

• Abnormal tumor vasculature hinders anti-cancer drug efficacy.
• Notch signaling is vital for blood vessel development but its precise role in vascular structure is unclear.

Purpose of the Study:

• To elucidate the role and mechanism of Notch signaling in tumor vascular structure formation.
• To investigate Notch signaling's impact on endothelial cells (ECs) and vascular integrity.

Main Methods:

• Investigated the effects of blocking and overactivating Notch signaling in endothelial cells.
• Utilized healthy mice models and neonatal mice.
• Analyzed tumor blood vessel basement membrane, blood perfusion, and barrier integrity (BRB, BBB).
• Examined the regulation of adhesion junctions (AJs) and the downstream gene Hspg2.

Main Results:

• Blocking Notch signaling obstructed tumor blood vessel basement membrane formation and reduced blood perfusion.
• Notch inhibition led to blood-retinal barrier and blood-brain barrier destruction in healthy mice.
• Notch overactivation increased tumor blood vessel basement membrane and perfusion, promoting smooth muscle cell recruitment.
• Notch signaling was confirmed to regulate EC adhesion junctions via Hspg2 expression.

Conclusions:

• Notch signaling critically regulates tumor vascular structure and integrity.
• Targeting Notch signaling presents a promising strategy for improving anti-cancer therapies and understanding vascular diseases.