Peritumor lymphatics induced by vascular endothelial growth factor-C exhibit abnormal function.
Vascular endothelial growth factor (VEGF)-C is known to induce hyperplasia in normal murine lymphatics and in peritumor lymphatics. Here, we examine the function of these hyperplastic peritumor lymphatics. Microlymphangiography of B16F10 melanomas growing in the murine dorsal skinfold chamber showed that the number of functional, draining lymphatics in the peritumor tissue of VEGF-C-overexpressing tumors was significantly greater than that in mock-transduced tumors (9.5 +/- 1.0 versus 6.3 +/- 0.4; n = 6; P < 0.05). Forty percent of functional lymphatics associated with VEGF-C-overexpressing tumors contained proliferating lymphatic endothelial cells. Surprisingly, these new, functional lymphatic vessels displayed a retrograde draining pattern, which indicates possible dysfunction of the intraluminal valves of these vessels.
Isaka
Naohide
N
E. L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Padera
Timothy P
TP
Hagendoorn
Jeroen
J
Fukumura
Dai
D
Jain
Rakesh K
RK
D000818:Animals; D002455:Cell Division / Q000502:physiology; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology*; D008220:Lymphography; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D018613:Microscopy, Confocal; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis / Q000502:physiology*
D042582:Vascular Endothelial Growth Factor C; C467483:vascular endothelial growth factor C, mouse