Absence of functional lymphatics within a murine sarcoma: a molecular and functional evaluation.
Despite a clinically recognized association between the lymphatics and metastasis, the biology of tumor-lymphatic interaction is not clearly understood. We report here that functional lymphatic capillaries are absent from the interior of a solid tumor, despite the presence within the tumor of the lymphangiogenic molecule vascular endothelial growth factor (VEGF)-C and endothelial cells bearing its receptor, VEGF receptor 3. Functional lymphatics, enlarged and VEGF receptor 3 positive, were detected in some tumors only at the tumor periphery (within 100 microm of the interface with normal tissue). We conclude that although lymphangiogenic factors are present, formation of functional lymphatic vessels is prevented, possibly due to collapse by the solid stress exerted by growing cancer cells.
Leu
A J
AJ
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Berk
D A
DA
Lymboussaki
A
A
Alitalo
K
K
Jain
R K
RK
D000818:Animals; D016228:Endothelial Growth Factors / Q000378:metabolism; D004729:Endothelium, Lymphatic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005453:Fluorescence; D017403:In Situ Hybridization; D008208:Lymphatic System / Q000033:anatomy & histology / Q000378:metabolism / Q000503:physiopathology*; D008220:Lymphography / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D012513:Sarcoma, Experimental / Q000473:pathology / Q000503:physiopathology*; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3
D016228:Endothelial Growth Factors; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D042582:Vascular Endothelial Growth Factor C; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040321:Vascular Endothelial Growth Factor Receptor-3