VEGFD/VEGFR2 axis induces the dedifferentiation of high endothelial venules and impairs lymphocyte homing.

ABSTRACT: High endothelial venules (HEVs) are important structures in lymph nodes (LNs) that mediate lymphocyte homing, and their dedifferentiation is a necessary step before LN metastasis. Whether vascular endothelial growth factor-related (VEGF-related) signaling, which plays an important role in LN metastasis, is involved in the dedifferentiation of HEVs remains unclear. Here, we confirmed increased expression of VEGFA, VEGFC, and VEGFD; HEV dedifferentiation; and impaired lymphocyte homing function in tumor-draining LNs (TDLNs). Furthermore, we demonstrated that tumor-secreted VEGFA induced lymphangiogenesis in TDLNs to promote premetastatic niche (PMN) formation; VEGFC promoted HEV proliferation but did not affect its lymphocyte homing function. Notably, we showed that VEGFD induced the dediffe

SUBMITTER: Yang W 

PROVIDER: S-EPMC12288975 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature