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Vascular endothelial growth factor-C expression correlates with lymph node localization of human melanoma metastases

  1. Cataldo Schietroma Ph.D.1,†,
  2. Francesca Cianfarani Ph.D.1,†,
  3. Pedro M. Lacal Ph.D.2,
  4. Teresa Odorisio Ph.D.1,
  5. Angela Orecchia Ph.D.1,
  6. Jean Kanitakis M.D.3,
  7. Stefania D'Atri Ph.D.2,
  8. Cristina M. Failla Ph.D.1,
  9. Giovanna Zambruno M.D.1,‡,*

Article first published online: 1 JUL 2003

DOI: 10.1002/cncr.11583

Issue

Cancer

Cancer

Volume 98, Issue 4, pages 789–797, 15 August 2003

Additional Information

How to Cite

Schietroma, C., Cianfarani, F., Lacal, P. M., Odorisio, T., Orecchia, A., Kanitakis, J., D'Atri, S., Failla, C. M. and Zambruno, G. (2003), Vascular endothelial growth factor-C expression correlates with lymph node localization of human melanoma metastases. Cancer, 98: 789–797. doi: 10.1002/cncr.11583

Author Information

  1. 1

    Molecular and Cell Biology Laboratory, Istituto Dermopatico Dell'Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico (IDI-IRCCS), Rome, Italy

  2. 2

    Clinical Pharmacology Laboratory, Istituto Dermopatico Dell'Immacolata-Istituto di Ricovero e Civa a Carattere Scientifico (IDI-IRCCS), Rome, Italy

  3. 3

    Laboratory of Dermatopathology, Department of Dermatology, Ed. Herriot Hospital, Lyon, France

  1. †

    The first two authors contributed equally to this article.

  2. ‡

    Fax: (011) 39-06-66464705

*Molecular and Cell Biology Laboratory, IDI-IRCCS, via Monti di Creta 104, 00167 Rome, Italy

Publication History

  1. Issue published online: 1 AUG 2003
  2. Article first published online: 1 JUL 2003
  3. Manuscript Accepted: 19 MAY 2003
  4. Manuscript Revised: 13 MAY 2003
  5. Manuscript Received: 10 APR 2003

Funded by

  • Ministero della Salute, Italy

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Keywords:

  • angiogenesis;
  • growth factors;
  • metastasis;
  • melanoma;
  • lymph nodes

Abstract

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. Cancer 2003;98:789–97. © 2003 American Cancer Society.

DOI 10.1002/cncr.11583

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