title: MET expression in melanoma correlates with a lymphangiogenic phenotype.
abstract: Melanomas contain high frequencies of tumorigenic cells and their tumorigenic capacity resides in several distinct subpopulations within melanoma. Since their metastatic potential is linked to their ability to recruit lymphatic vessels, we aimed at identifying lymphangiogenic subpopulations by comparative in vitro analysis of single cell clones derived from a melanoma of a single patient. Selected lymphangiogenic clones were then grafted into severe combined immunodeficient mice, where they induced lymphangiogenesis and metastasized into sentinel nodes, whereas non-lymphangiogenic clones from the same patient did not metastasize. Transcriptome analysis revealed high expression of vascular endothelial growth factor C (VEGF-C) and platelet derived growth factor C (PDGF-C) as well as of the met proto-oncogene (MET) and its targets to be associated with this lymphangiogenic phenotype. Screening of a set of independently isolated melanoma cell lines from other patients confirmed this association between expression of high levels of MET and of VEGF-C and PDGF-C. Hence, we provide a model to screen for the lymphangiogenic potential of tumor cells. We show that the lymphangiogenic potential is heterogeneously distributed among melanoma cells within one given tumor and is associated with activation of MET signaling.
authors.affiliation: Skin and Endothelium Research Division, Department of Dermatology, Medical University of Vienna, Währingergürtel 18-20, Vienna 1090, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Swoboda
authors.forename: Oliver
authors.initials: O
authors.lastname: Schanab
authors.forename: Stefanie
authors.initials: S
authors.lastname: Tauber
authors.forename: Martin
authors.initials: M
authors.lastname: Bilban
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.forename: Peter
authors.initials: P
authors.lastname: Petzelbauer
authors.forename: Mario
authors.initials: M
authors.lastname: Mikula
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D042583:Lymphangiogenesis / Q000235:genetics*; D008207:Lymphatic Metastasis; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D008222:Lymphokines; C000715470:MAS1 protein, human; D010982:Platelet-Derived Growth Factor; D000090063:Proto-Oncogene Mas; D042582:Vascular Endothelial Growth Factor C; C411423:platelet-derived growth factor C; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met