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- Title
Epidermal Growth Factor Facilitates Melanoma Lymph Node Metastasis by Influencing Tumor Lymphangiogenesis.
- Authors
Bracher, Andreas; Cardona, Ana Soler; Tauber, Stefanie; Fink, Astrid M; Steiner, Andreas; Pehamberger, Hubert; Niederleithner, Heide; Petzelbauer, Peter; Gröger, Marion; Loewe, Robert
- Abstract
Alterations in epidermal growth factor (EGF) expression are known to be of prognostic relevance in human melanoma, but EGF-mediated effects on melanoma have not been extensively studied. As lymph node metastasis usually represents the first major step in melanoma progression, we were trying to identify a potential role of primary tumor-derived EGF in the mediation of melanoma lymph node metastases. Stable EGF knockdown (EGFkd) in EGF-high (M24met) and EGF-low (A375) expressing melanoma cells was generated. Only in EGF-high melanoma cells, EGFkd led to a significant reduction of lymph node metastasis and primary tumor lymphangiogenesis in vivo, as well as impairment of tumor cell migration in vitro. Moreover, EGF-induced sprouting of lymphatic but not of blood endothelial cells was abolished using supernatants of M24met EGFkd cells. In addition, M24met EGFkd tumors showed reduced vascular endothelial growth factor-C (VEGF-C) expression levels. Similarly, in human primary melanomas, a direct correlation between EGF/VEGF-C and EGF/Prox-1 expression levels was found. Finally, melanoma patients with lymph node micrometastases undergoing sentinel node biopsy were found to have significantly elevated EGF serum levels as compared with sentinel lymph node-negative patients. Our data indicate that tumor-derived EGF is important in mediating melanoma lymph node metastasis.
- Subjects
EPIDERMAL growth factor; MELANOMA; LYMPH node cancer; METASTASIS; LYMPHATIC tumors; GENE expression; CANCER invasiveness
- Publication
Journal of Investigative Dermatology, 2013, Vol 133, Issue 1, p230
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/jid.2012.272