A KDR-binding peptide (ST100,059) can block angiogenesis, melanoma tumor growth and metastasis in vitro and in vivo

  • Authors:
    • Luca Rastelli
    • Maria Luisa Valentino
    • Melissa Corso Minderman
    • Judith Landin
    • Uriel M. Malyankar
    • Mary K. Lescoe
    • Richard Kitson
    • Kenneth Brunson
    • Lina Souan
    • Salvatore Forenza
    • Ronald H. Goldfarb
    • Shafaat A. Rabbani
  • View Affiliations

  • Published online on: May 11, 2011     https://doi.org/10.3892/ijo.2011.1040
  • Pages: 401-408
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Abstract

A major goal of treatment strategies for cancer is the development of agents which can block primary tumor growth and development as well as the progression of tumor metastasis without any treatment associated side effects. Using mini peptide display (MPD) technology, we generated peptides that can bind to the human vascular endothelial growth factor (VEGF) receptor KDR. These peptides were evaluated for their ability to block angiogenesis, tumor growth and metastasis in vitro and in vivo. A D-amino acid peptide with high serum stability (ST100,059) was found to have the most potent activity in vitro as indicated by inhibition of VEGF stimulation of endothelial cells. It was also found to be the most active of the series in blocking VEGF-mediated activity in vivo, as measured in Matrigel-filled angioreactors implanted in mice. ST100,059 blocks VEGF-induced MAPK phosphorylation, as well as inhibits VEGF-induced changes in gene expression in HUVEC cells. In in vivo studies, treatment of female C57BL/6 mice inoculated with B16 mouse melanoma cells with ST100,059 resulted in a dose-dependent decrease in tumor volume and lung metastasis as compared to control groups of animals receiving vehicle alone. These studies demonstrate that by using MPD, peptides can be identified with enhanced affinity relative to those discovered using phage display. Based on these studies we have identified one such peptide ST100,059 which can effectively block tumor growth and metastasis due to its anti-angiogenic effects and ability to block intracellular signaling pathways involved in tumor progression.

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August 2011
Volume 39 Issue 2

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

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Spandidos Publications style
Rastelli L, Valentino ML, Minderman MC, Landin J, Malyankar UM, Lescoe MK, Kitson R, Brunson K, Souan L, Forenza S, Forenza S, et al: A KDR-binding peptide (ST100,059) can block angiogenesis, melanoma tumor growth and metastasis in vitro and in vivo. Int J Oncol 39: 401-408, 2011
APA
Rastelli, L., Valentino, M.L., Minderman, M.C., Landin, J., Malyankar, U.M., Lescoe, M.K. ... Rabbani, S.A. (2011). A KDR-binding peptide (ST100,059) can block angiogenesis, melanoma tumor growth and metastasis in vitro and in vivo. International Journal of Oncology, 39, 401-408. https://doi.org/10.3892/ijo.2011.1040
MLA
Rastelli, L., Valentino, M. L., Minderman, M. C., Landin, J., Malyankar, U. M., Lescoe, M. K., Kitson, R., Brunson, K., Souan, L., Forenza, S., Goldfarb, R. H., Rabbani, S. A."A KDR-binding peptide (ST100,059) can block angiogenesis, melanoma tumor growth and metastasis in vitro and in vivo". International Journal of Oncology 39.2 (2011): 401-408.
Chicago
Rastelli, L., Valentino, M. L., Minderman, M. C., Landin, J., Malyankar, U. M., Lescoe, M. K., Kitson, R., Brunson, K., Souan, L., Forenza, S., Goldfarb, R. H., Rabbani, S. A."A KDR-binding peptide (ST100,059) can block angiogenesis, melanoma tumor growth and metastasis in vitro and in vivo". International Journal of Oncology 39, no. 2 (2011): 401-408. https://doi.org/10.3892/ijo.2011.1040