An autocrine loop directed by the vascular endothelial growth factor promotes invasiveness of human melanoma cells

  • Authors:
    • Pedro Miguel Lacal
    • Federica Ruffini
    • Elena Pagani
    • Stefania D'Atri
  • View Affiliations

  • Published online on: December 1, 2005     https://doi.org/10.3892/ijo.27.6.1625
  • Pages: 1625-1632
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Abstract

The vascular endothelial growth factor-A (VEGF-A) is a cytokine that promotes angiogenesis through the activation of two tyrosine kinase receptors, VEGFR-1 and VEGFR-2, on vascular endothelial cells. Moreover, several experimental evidences indicate that VEGF-A may also play a role in tumor progression by acting on neoplastic cells expressing VEGFRs. In this study we show that human melanoma cells that simultaneously produce VEGF-A and express VEGFRs exhibit a higher spontaneous ability to invade the extracellular matrix (ECM) than melanoma cells not expressing either VEGF-A or VEGFRs. Exposure of VEGFR expressing melanoma cells to exogenous VEGF-A further increases their ability to invade the ECM. Moreover, an inhibitor of VEGFR tyrosine kinase activity is able to abrogate VEGF-A-induced stimulation of ECM invasion. A cell clone (13443/N2) derived from a VEGF-A responsive melanoma cell line and expressing high levels of VEGFR-2 invades the ECM eight-fold more efficiently than a cell clone derived from the same cell line and expressing extremely low levels of the receptor. Exposure of 13443/N2 cells to VEGF-E, which selectively binds and activates VEGFR-2, increases their ability to invade the ECM. Finally, the expression of the VEGF-A mRNA antisense sequence in 13443/N2 cells markedly reduces the release of VEGF-A and ECM invasion. In conclusion, our data show for the first time that a VEGF-A-driven autocrine loop promotes human melanoma cell ability to invade the ECM, and strongly support the hypothesis that activation of VEGFR-2 plays a primary role in this process.

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December 2005
Volume 27 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Lacal, P.M., Ruffini, F., Pagani, E., & D'Atri, S. (2005). An autocrine loop directed by the vascular endothelial growth factor promotes invasiveness of human melanoma cells. International Journal of Oncology, 27, 1625-1632. https://doi.org/10.3892/ijo.27.6.1625
MLA
Lacal, P. M., Ruffini, F., Pagani, E., D'Atri, S."An autocrine loop directed by the vascular endothelial growth factor promotes invasiveness of human melanoma cells". International Journal of Oncology 27.6 (2005): 1625-1632.
Chicago
Lacal, P. M., Ruffini, F., Pagani, E., D'Atri, S."An autocrine loop directed by the vascular endothelial growth factor promotes invasiveness of human melanoma cells". International Journal of Oncology 27, no. 6 (2005): 1625-1632. https://doi.org/10.3892/ijo.27.6.1625