Preexisting lymphatic endothelium but not endothelial progenitor cells are essential for tumor lymphangiogenesis and lymphatic metastasis.
Endothelial progenitor cells have been shown to contribute to angiogenesis in various tumor models. Here, we have studied the relative contributions of bone marrow (BM)-derived endothelial progenitors and pre-existing lymphatic vessels to tumor lymphangiogenesis. We did not find significant incorporation of genetically marked BM-derived cells in lymphatic vessels during tumor- or vascular endothelial growth factor C-induced lymphangiogenesis. The degree of tumor lymphangiogenesis correlated with lymphatic vessel density in the peritumoral area, and despite tumor lymphangiogenesis, lymphatic metastasis failed to occur in gene-targeted vascular endothelial growth factor C(+/-) mice that have hypoplasia of the lymphatic network. Our data demonstrate that during tumor lymphangiogenesis and cancer cell dissemination via the lymphatics, the newly formed lymphatic vessels sprout from the pre-existing local lymphatic network with little if any incorporation of BM-derived endothelial progenitor cells.
He
Yulong
Y
Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, Helsinki University Central Hospital, and Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Rajantie
Iiro
I
Ilmonen
Maritta
M
Makinen
Taija
T
Karkkainen
Marika J
MJ
Haiko
Paula
P
Salven
Petri
P
Alitalo
Kari
K
D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D042783:Endothelial Cells / Q000473:pathology; D004729:Endothelium, Lymphatic / Q000473:pathology*; D042583:Lymphangiogenesis / Q000502:physiology*; D008207:Lymphatic Metastasis; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013234:Stem Cells / Q000473:pathology*