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- Title
Active interaction of human A375 melanoma cells with the lymphatics in vivo.
- Authors
Papoutsi, Maria; Siemeister, Gerhard; Weindel, Karin; Tomarev, Stanislav I.; Kurz, Haymo; Schächtele, Christoph; Martiny-Baron, Georg; Christ, Bodo; Marméz, Dieter; Wilting, Jörg
- 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.
- Subjects
LYMPHATIC cancer; NEUROENDOCRINE tumors; NUCLEIC acids; GENETIC transformation; CANCER cells; GROWTH factors; IMMUNE system
- Publication
Histochemistry & Cell Biology, 2000, Vol 114, Issue 5, p373
- ISSN
0948-6143
- Publication type
Article
- DOI
10.1007/s004180000204