Journal ArticleDOI
Active interaction of human A375 melanoma cells with the lymphatics in vivo.
Maria Papoutsi,Gerhard Siemeister,Karin Weindel,Stanislav I. Tomarev,Haymo Kurz,Christoph Schächtele,Georg Martiny-Baron,Bodo Christ,Dieter Marmé,Jörg Wilting +9 more
TLDR
Tumor-induced lymphangiogenesis seems to be dependent to some extent on VEGF-C/flt4 interactions, but invasion of lymphatics seems to been a distinct mechanism.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.read more
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Tumor-Associated Macrophages Express Lymphatic Endothelial Growth Factors and Are Related to Peritumoral Lymphangiogenesis
Sebastian F. Schoppmann,Peter Birner,Johannes Stöckl,Romana Kalt,Robert Ullrich,Carola Caucig,Ernst Kriehuber,Katalin Nagy,Kari Alitalo,Dontscho Kerjaschki +9 more
TL;DR: V EGF-C- and VEGF-D-expressing TAMs play a novel role in peritumoral lymphangiogenesis and subsequent dissemination in human cancer.
Journal Article
LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis.
Carla Mouta Carreira,Selim M. Nasser,Emmanuelle di Tomaso,Timothy P. Padera,Yves Boucher,Stanislav I. Tomarev,Rakesh K. Jain +6 more
TL;DR: It is demonstrated that lymphatics are abundant in cirrhosis by combining LYVE-1 and Prox 1 (a transcription factor) immunohistochemistry and proposed a novel approach to identify lymphatics in human and murine liver.
Journal ArticleDOI
Lymphatic endothelium: a new frontier of metastasis research.
TL;DR: The vascular endothelium is a dynamic tissue with many active functions, and recent developments have highlighted the importance of lymphatic ECs, and they could become the next focus for angiogenesis and metastasis research.
Journal ArticleDOI
Lymphangiogenesis and lymphangiodysplasia: From molecular to clinical lymphology
TL;DR: Recent advances in “molecular lymphology” are elucidating the poorly understood development, physiology, and pathophysiology of the neglected lymphatic vasculature, which should lead not only to earlier detection and more rational classification of lymphatic disease but also to better therapeutic approaches.
Journal ArticleDOI
The transcription factor Prox1 is a marker for lymphatic endothelial cells in normal and diseased human tissues
Jörg Wilting,Maria Papoutsi,Bodo Christ,Kypros H. Nicolaides,Constantin von Kaisenberg,J. Borges,G. Björn Stark,Kari Alitalo,Stanislav I. Tomarev,Charlotte M. Niemeyer,Jochen Rössler +10 more
TL;DR: It is shown that Prox1 is a reliable marker for LECs in normal and pathologic human tissues, coexpressed with VEGFR‐3 and CD31, which are less reliable markers for L ECs and BECs, respectively, because exceptions from their normal expression patterns are found in pathologic tissues.
References
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Journal ArticleDOI
A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases.
Vladimir Joukov,Katri Pajusola,Arja Kaipainen,Dmitri Chilov,Isto Lahtinen,Eola Kukk,Olli Saksela,Nisse Kalkkinen,Kari Alitalo +8 more
TL;DR: VEGF‐C is a novel regulator of endothelia, and its effects may extend beyond the lymphatic system, where Flt4 is expressed.