Vascular endothelial growth factor-C stimulates the migration and proliferation of Kaposi's sarcoma cells

Serena Marchiò, Luca Primo, Marco Pagano, Giorgio Palestro, Adriana Albini, Tanja Veikkola, Ilaria Cascone, Kari Alitalo, Federico Bussolino

Research output: Contribution to journalArticle

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Abstract

Recent evidence suggesting vascular endothelial growth factor-C (VEGF- C), which is a regulator of lymphatic and vascular endothelial development, raised the question whether this molecule could be involved in Kaposi's sarcoma (KS), a strongly angiogenic and inflammatory tumor often associated with infection by human immunodeficiency virus-1. This disease is characterized by the presence of a core constituted of three main populations of 'spindle' cells, having the features of lymphatic/vascular endothelial cells, macrophagic/dendritic cells, and of a mixed macrophage-endothelial phenotype. In this study we evaluated the biological response of KS cells to VEGF-C, using an immortal cell line derived from a KS lesion (KS IMM), which retains most features of the parental tumor and can induce KS-like sarcomas when injected subcutaneously in nude mice. We show that VEGFR-3, the specific receptor for VEGF-C, is expressed by KS IMM cells grown in vitro and in vivo. In vitro, VEGF-C induces the tyrosine phosphorylation of VEGFR-2, a receptor also for VEGF-A, as well as that of VEGFR-3. The activation of these two receptors in KS IMM cells is followed by a dose-responsive mitogenic and motogenic response. The stimulation of KS IMM cells with a mutant VEGF-C unable to bind and activate VEFGR-2 resulted in no proliferative response and in a weak motogenic stimulation, suggesting that VEGFR-2 is essential in transducing a proliferative signal and cooperates with VEGFR-3 in inducing cell migration. Our data add new insights on the pathogenesis of KS, suggesting that the involvement of endothelial growth factors may not only determine KS-associated angiogenesis, but also play a critical role in controlling KS cell growth and/or migration and invasion.

Original languageEnglish
Pages (from-to)27617-27622
Number of pages6
JournalJournal of Biological Chemistry
Volume274
Issue number39
DOIs
Publication statusPublished - Sep 24 1999

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Vascular Endothelial Growth Factor C
Kaposi's Sarcoma
Vascular Endothelial Growth Factor Receptor-3
Vascular Endothelial Growth Factor Receptor-2
Tumors
Cells
Endothelial Growth Factors
Phosphorylation
Macrophages
Endothelial cells
Cell growth
Viruses
Vascular Endothelial Growth Factor A
Tyrosine
Chemical activation
Endothelial Cells
Molecules
Nude Mice
Sarcoma
Dendritic Cells

ASJC Scopus subject areas

  • Biochemistry

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Vascular endothelial growth factor-C stimulates the migration and proliferation of Kaposi's sarcoma cells. / Marchiò, Serena; Primo, Luca; Pagano, Marco; Palestro, Giorgio; Albini, Adriana; Veikkola, Tanja; Cascone, Ilaria; Alitalo, Kari; Bussolino, Federico.

In: Journal of Biological Chemistry, Vol. 274, No. 39, 24.09.1999, p. 27617-27622.

Research output: Contribution to journalArticle

Marchiò, Serena ; Primo, Luca ; Pagano, Marco ; Palestro, Giorgio ; Albini, Adriana ; Veikkola, Tanja ; Cascone, Ilaria ; Alitalo, Kari ; Bussolino, Federico. / Vascular endothelial growth factor-C stimulates the migration and proliferation of Kaposi's sarcoma cells. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 39. pp. 27617-27622.
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