Human melanoma cells secrete and respond to placenta growth factor and vascular endothelial growth factor

Pedro M. Lacal, Cristina M. Failla, Elena Pagani, Teresa Odorisio, Cataldo Schietroma, Sabrina Falcinelli, Giovanna Zambruno, Stefania D'Atri

Research output: Contribution to journalArticle

Abstract

The vascular endothelial growth factor is produced by a large variety of human tumors, including melanoma, in which it appears to play an important role in the process of tumor-induced angiogenesis. Little information is available on the role of placenta growth factor, a member of the vascular endothelial growth factor family of cytokines, in tumor angiogenesis, even though placenta growth factor/vascular endothelial growth factor heterodimers have been recently isolated from tumor cells. To investigate the role of placenta growth factor and vascular endothelial growth factor homodimers and heterodimers in melanoma angiogenesis and growth, 19 human melanoma cell lines derived from primary or metastatic tumors were characterized for the expression of these cytokines and their receptors. Release of placenta growth factor and vascular endothelial growth factor polypeptides into the supernatant of human melanoma cells was demonstrated. Reverse transcriptase polymerase chain reaction analysis showed the presence of mRNAs encoding at least three different vascular endothelial growth factor isoforms (VEGF121, VEGF165, and VEGF189) and transcripts for two placenta growth factor isoforms (PlGF-1 and PlGF-2) in human melanoma cells. In addition, placenta growth factor expression in human melanoma in vivo was detected by immunohistochemical staining of tumor specimens. Both primary and metastatic melanoma cells were found to express the mRNAs encoding for vascular endothelial growth factor and placenta growth factor receptors (KDR, Flt-1, neuropilin-1, and neuropilin-2), and exposure of melanoma cells to these cytokines resulted in a specific proliferative response, supporting the hypothesis of a role of these angiogenic factors in melanoma growth.

Original languageEnglish
Pages (from-to)1000-1007
Number of pages8
JournalJournal of Investigative Dermatology
Volume115
Issue number6
DOIs
Publication statusPublished - 2000

Keywords

  • Angiogenesis
  • Melanoma progression

ASJC Scopus subject areas

  • Dermatology

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