MET expression in melanoma correlates with a lymphangiogenic phenotype.

Human Molecular Genetics
Alexander SwobodaMario Mikula

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...Continue Reading

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Citations

Aug 2, 2014·The Journal of Investigative Dermatology·Magdalena HeinzPeter Petzelbauer
Feb 2, 2016·The Journal of Investigative Dermatology·Emmi PuujalkaPeter Petzelbauer
Jan 25, 2014·Asia-Pacific Journal of Clinical Oncology·Samantha BowyerMichael Millward
Nov 18, 2016·Scientific Reports·Birgit SchützMario Mikula
Mar 3, 2019·International Journal of Molecular Sciences·Katharina KinslechnerMario Mikula
Feb 24, 2021·Journal of Cancer Research and Clinical Oncology·Tomonori SasahiraTadaaki Kirita

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