lymphangiogenesis

Lymphangiogenesis is the growth of new lymphatic vessels from pre-existing lymphatic vessels or lymphatic endothelial cells. It contributes to embryonic development, tissue repair, and various diseases. In mammals, the lymphatic system arises when lymphatic endothelial progenitors bud from veins and, under the control of transcription factors such as PROX1, SOX18, and FOXC2, establish a network of lymphatic vessels. These sprouts mature into lymphatic capillaries and collecting vessels that drain interstitial fluid, ferry immune cells, and absorb dietary lipids in the gut via lacteals.

The principal molecular drivers are vascular endothelial growth factors VEGF-C and VEGF-D signaling through the VEGFR-3 (FLT4) receptor. Proteolytic processing of VEGF-C enhances its activity. Downstream signaling promotes lymphatic endothelial cell proliferation, migration, and tube formation. Additional regulators include PROX1 maintaining lymphatic identity, and the Angiopoietins/Tie2 axis, inflammatory mediators, and macrophage-derived cues that support sprouting, maturation, and vessel remodeling.

Physiological roles include fluid drainage, immune surveillance, and lipid absorption; in the intestine, lacteals are specialized lymphatics for chylomicron uptake. Pathologically, lymphangiogenesis can facilitate cancer metastasis through lymphatic routes, and inadequate lymphatic growth or damage can cause lymphedema. Inflammation and tissue injury often induce lymphangiogenesis as part of repair, sometimes with dual effects on disease progression.

Clinical relevance and therapy: modulation of lymphangiogenesis is explored to treat lymphedema, promote transplant and wound healing, or limit cancer spread. Therapeutic approaches target VEGF-C/-D, VEGFR-3 signaling, or related pathways, with attention to balancing beneficial drainage against potential risks of promoting tumor spread. Imaging techniques such as lymphangiography and lymphoscintigraphy aid assessment.