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A small-molecule RGD-integrin antagonist inhibits cell adhesion, cell migration and induces anoikis in glioblastoma cells

  • Authors:
    • Marika A. Russo
    • Mayra Paolillo
    • Yuly Sanchez-Hernandez
    • Daniela Curti
    • Emilio Ciusani
    • Massimo Serra
    • Lino Colombo
    • Sergio Schinelli
  • View Affiliations / Copyright

    Affiliations: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA, Department of Drug Sciences, University of Pavia, I-27100 Pavia, Italy, Department of Biology and Biotechnology ‘Lazzaro Spallanzani’, University of Pavia, I-27100 Pavia, Italy, Carlo Besta Neurological Institute, I-20133 Milan, Italy
    Copyright: © Russo et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 83-92
    |
    Published online on: November 20, 2012
       https://doi.org/10.3892/ijo.2012.1708
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Abstract

In cancer cells integrins modulate important cellular events that regulate the metastasic cascade which involves detachment from the tumor mass, dissemination and attachment to the oncogenic niche. The α5β1, αvβ3 and αvβ5 integrins are widely expressed in different cancer types and recognize the tripeptide Arg-Gly-Asp (RGD) motif present in several extracellular matrix proteins. In human glioblastoma, αvβ3 integrin expression correlates with tumor grade, suggesting that this integrin may play a crucial role in the highly infiltrative behavior of high grade gliomas. However, few selective RGD-like antagonists have been developed and few studies have investigated their effects in in vitro models of human glioblastoma. In this study, we investigated several cellular effects and the underlying molecular mechanisms exerted by a new small-molecule RGD antagonist, 1a-RGD, in the U251 and U373 human glioblastoma cell lines. Treatment with 1a-RGD (20 µM) demonstrated a weak effect on cell viability and cell proliferation but strongly inhibited cell attachment and cell migration together with actin cytoskeleton disassembly. Prolonged 1a-RGD treatment (72 h) induced anoikis, assessed by Annexin staining and nucleosome assay, particularly in the detached cells. When integrin-linked transduction pathways were investigated, 1aRGD was found to exert a marked reduction in focal adhesion kinase (FAK) phosphorylation without affecting the AKT- and ERK-dependent pathways. Our data indicate that 1a-RGD, probably via modulation of the FAK-dependent pathway, inhibits cell migration and attachment and induces anoikis in glioblastoma cells. This novel finding suggests that the development of an RGD-like molecule may represent a promising tool for the pharmacological approach aimed at reducing the malignancy of glioblastoma cells.
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Copy and paste a formatted citation
Spandidos Publications style
Russo MA, Paolillo M, Sanchez-Hernandez Y, Curti D, Ciusani E, Serra M, Colombo L and Schinelli S: A small-molecule RGD-integrin antagonist inhibits cell adhesion, cell migration and induces anoikis in glioblastoma cells. Int J Oncol 42: 83-92, 2013.
APA
Russo, M.A., Paolillo, M., Sanchez-Hernandez, Y., Curti, D., Ciusani, E., Serra, M. ... Schinelli, S. (2013). A small-molecule RGD-integrin antagonist inhibits cell adhesion, cell migration and induces anoikis in glioblastoma cells. International Journal of Oncology, 42, 83-92. https://doi.org/10.3892/ijo.2012.1708
MLA
Russo, M. A., Paolillo, M., Sanchez-Hernandez, Y., Curti, D., Ciusani, E., Serra, M., Colombo, L., Schinelli, S."A small-molecule RGD-integrin antagonist inhibits cell adhesion, cell migration and induces anoikis in glioblastoma cells". International Journal of Oncology 42.1 (2013): 83-92.
Chicago
Russo, M. A., Paolillo, M., Sanchez-Hernandez, Y., Curti, D., Ciusani, E., Serra, M., Colombo, L., Schinelli, S."A small-molecule RGD-integrin antagonist inhibits cell adhesion, cell migration and induces anoikis in glioblastoma cells". International Journal of Oncology 42, no. 1 (2013): 83-92. https://doi.org/10.3892/ijo.2012.1708
Copy and paste a formatted citation
x
Spandidos Publications style
Russo MA, Paolillo M, Sanchez-Hernandez Y, Curti D, Ciusani E, Serra M, Colombo L and Schinelli S: A small-molecule RGD-integrin antagonist inhibits cell adhesion, cell migration and induces anoikis in glioblastoma cells. Int J Oncol 42: 83-92, 2013.
APA
Russo, M.A., Paolillo, M., Sanchez-Hernandez, Y., Curti, D., Ciusani, E., Serra, M. ... Schinelli, S. (2013). A small-molecule RGD-integrin antagonist inhibits cell adhesion, cell migration and induces anoikis in glioblastoma cells. International Journal of Oncology, 42, 83-92. https://doi.org/10.3892/ijo.2012.1708
MLA
Russo, M. A., Paolillo, M., Sanchez-Hernandez, Y., Curti, D., Ciusani, E., Serra, M., Colombo, L., Schinelli, S."A small-molecule RGD-integrin antagonist inhibits cell adhesion, cell migration and induces anoikis in glioblastoma cells". International Journal of Oncology 42.1 (2013): 83-92.
Chicago
Russo, M. A., Paolillo, M., Sanchez-Hernandez, Y., Curti, D., Ciusani, E., Serra, M., Colombo, L., Schinelli, S."A small-molecule RGD-integrin antagonist inhibits cell adhesion, cell migration and induces anoikis in glioblastoma cells". International Journal of Oncology 42, no. 1 (2013): 83-92. https://doi.org/10.3892/ijo.2012.1708
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