BMP4 and neoplasm: These changes coincide with the remodeling of HEVs from thick-walled endothelial vessels with a small lumen to thin-walled vessels with a larger lumen, causing a functional shift away from lymphocyte recruitment in favor of greater blood flow that is conducive to metastatic tumor cell arrival.75 Bone morphogenetic protein-4 (BMP-4) loss has also been linked to this thin-walled HEV remodeling,76 as has CCL21 dysregulation in perivascular FRCs and associated CCL21-saturated lymphocyte accumulation.77