Vascular endothelial growth factor-C expression correlates with lymph node localization of human melanoma metastases.
BACKGROUND
Melanoma metastasizes by different mechanisms comprising direct invasion of the surrounding tissue and spreading via the lymphatic or vascular system. Despite their clinical relevance, the molecular mechanisms that guide the route of spreading and localization of the metastases in different tissues are not well known. Recent studies in different tumor types have shown that vascular endothelial growth factor-C (VEGF-C), which displays a high specificity for lymphatic endothelium, is involved in tumor-induced lymphangiogenesis and lymphatic metastatic spread. The authors studied the expression of VEGF-C in cultured human melanoma cells derived from cutaneous and lymph node metastases as well as in metastatic melanoma tissue specimens to assess a possible involvement of this growth factor in lymph node localization of melanoma metastases.


METHODS
VEGF-C expression was evaluated in vitro on human melanoma cell lines established from cutaneous and lymph node metastasis specimens by reverse transcriptase-polymerase chain reaction, Northern blot analysis, and immunofluorescence analysis. Immunohistochemical analysis of 42 tissue specimens of melanoma metastases and 10 tissue specimens of primary skin melanomas was also performed.


RESULTS
Preferential expression of VEGF-C was detected in lymph node-derived tumor cell lines at both the mRNA and protein levels. The association between VEGF-C production and lymph node localization of metastases was confirmed by the in vivo analysis. In addition, analysis of 10 patients, from whom specimens of both the primary skin melanoma and melanoma metastases were available, indicated a correlation between VEGF-C expression in the primary tumor and lymph node localization of metastases.


CONCLUSIONS
The findings of the current study demonstrate that VEGF-C expression is correlated with localization of melanoma metastases in the lymph nodes and suggest that VEGF-C expression in primary skin melanoma may be predictive of lymph node metastatic dissemination.
Schietroma
Cataldo
C
Molecular and Cell Biology Laboratory, Istituto Dermopatico Dell'Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico (IDI-IRCCS), Rome, Italy.
Cianfarani
Francesca
F
Lacal
Pedro M
PM
Odorisio
Teresa
T
Orecchia
Angela
A
Kanitakis
Jean
J
D'Atri
Stefania
S
Failla
Cristina M
CM
Zambruno
Giovanna
G
D015152:Blotting, Northern; D015139:Blotting, Southern; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000737:chemistry*; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000737:chemistry* / Q000556:secondary*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000737:chemistry; D012878:Skin Neoplasms / Q000737:chemistry / Q000473:pathology*; D014407:Tumor Cells, Cultured; D042582:Vascular Endothelial Growth Factor C
D016228:Endothelial Growth Factors; D012333:RNA, Messenger; D042582:Vascular Endothelial Growth Factor C