The study investigates the structural basis of tumor vessel leakiness, a phenomenon crucial for certain cancer therapies. Researchers compared blood vessels in MCA-IV mouse mammary carcinomas, known for their high leakiness, to less leaky tumors and normal mammary glands. Using various staining methods and electron microscopy, they found that all tumor vessels had a defective endothelial monolayer characterized by disorganized, loosely connected, branched, overlapping, or sprouting endothelial cells. These cells exhibited intercellular openings (mean diameter 1.7 μm) and transcellular holes (mean diameter 0.6 μm), with the former being more numerous and contributing significantly to the leakiness. The study concludes that these openings between disorganized endothelial cells are responsible for tumor vessel leakiness and may facilitate the delivery of therapeutic agents to tumor cells.The study investigates the structural basis of tumor vessel leakiness, a phenomenon crucial for certain cancer therapies. Researchers compared blood vessels in MCA-IV mouse mammary carcinomas, known for their high leakiness, to less leaky tumors and normal mammary glands. Using various staining methods and electron microscopy, they found that all tumor vessels had a defective endothelial monolayer characterized by disorganized, loosely connected, branched, overlapping, or sprouting endothelial cells. These cells exhibited intercellular openings (mean diameter 1.7 μm) and transcellular holes (mean diameter 0.6 μm), with the former being more numerous and contributing significantly to the leakiness. The study concludes that these openings between disorganized endothelial cells are responsible for tumor vessel leakiness and may facilitate the delivery of therapeutic agents to tumor cells.