title: Active interaction of human A375 melanoma cells with the lymphatics in vivo.
abstract: We have used the avian chorioallantoic membrane (CAM) to study the interaction of tumor cells with the lymphatics in vivo. The vascular endothelial growth factor-C (VEGF-C) has been shown to be lymphangiogenic. We have therefore grown VEGF-C-expressing human A375 melanoma cells on the CAM. These tumors induced numerous lymphatics at the invasive front, and compressed or destroyed VEGF receptor (R)-3-positive lymphatics were observed within the solid tumors. The lymphatics in the CAM and in the A375 melanomas could also be demonstrated with an antibody against Prox 1, a highly specific marker of lymphatic endothelial cells. Proliferation studies revealed a BrdU labeling index of 11.6% of the lymphatic endothelial cells in the tumors and at their margins. A great number of melanoma cells invaded the lymphatics. Such interactions were not observed with VEGF-C-negative Malme 3 M melanoma cells. Lymphangiogenesis was inhibited to some extent when A375 melanoma cells were transfected with cDNA encoding soluble VEGFR-3 (sflt4), and the BrdU labeling index of the lymphatics in these tumors was 3.9%. Invasion of lymphatics and growth of blood vascular capillaries were not inhibited by the transfection. Therefore, tumor-induced lymphangiogenesis seems to be dependent to some extent on VEGF-C/flt4 interactions, but invasion of lymphatics seems to be a distinct mechanism.
authors.affiliation: Anatomisches Institut, Albert-Ludwigs-Universität, Lehrstuhl II, Albertstrasse 17, 79104 Freiburg i. Br., Germany.
authors.forename: M
authors.initials: M
authors.lastname: Papoutsi
authors.forename: G
authors.initials: G
authors.lastname: Siemeister
authors.forename: K
authors.initials: K
authors.lastname: Weindel
authors.forename: S I
authors.initials: SI
authors.lastname: Tomarev
authors.forename: H
authors.initials: H
authors.lastname: Kurz
authors.forename: C
authors.initials: C
authors.lastname: Schächtele
authors.forename: G
authors.initials: G
authors.lastname: Martiny-Baron
authors.forename: B
authors.initials: B
authors.lastname: Christ
authors.forename: D
authors.initials: D
authors.lastname: Marmé
authors.forename: J
authors.initials: J
authors.lastname: Wilting
mesh_terms: D000481:Allantoin / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division; D002467:Cell Nucleus / Q000648:ultrastructure; D002642:Chick Embryo; D003370:Coturnix; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008208:Lymphatic System / Q000473:pathology* / Q000648:ultrastructure; D008546:Melanoma, Experimental / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008819:Mice, Nude; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D040321:Vascular Endothelial Growth Factor Receptor-3; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; D017978:Receptors, Growth Factor; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D000481:Allantoin; D020794:Receptor Protein-Tyrosine Kinases; D040321:Vascular Endothelial Growth Factor Receptor-3