Metalloproteinase dependent reduction of cell surface cluster determinants upon the induction of apoptosis

  • Authors:
    • Albert Magro
    • Alice Magro
    • Sirish Shrestha
    • Kathy Brundage
    • Gary Rankin
  • View Affiliations

  • Published online on: March 13, 2014     https://doi.org/10.3892/ijo.2014.2344
  • Pages: 1539-1550
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

LN18 glioblastoma cells were used as a model to examine changes in surface cluster determinants (CDs) as the cells undergo apoptosis. LN18 cells proceeding through apoptosis manifested a decrease in cell adhesion molecules, growth factor receptors and other surface proteins. Apoptosis was induced by MK886, a known FLAP and PPAR-α inhibitor, or staurosporine, a known inhibitor of protein kinases including protein kinase C (PKC). The detection and decrease of surface CDs were observed by flow cytometry using CD-specific primary antibodies followed by secondary antibodies conjugated to phycoerythrin. It was determined that there was an apoptotic induced decrease of α and β integrin determinants and the growth factor receptors EGFR and IGF1R. The MHC-1 cell surface marker HLA-ABC was also reduced in the apoptotic cells. The level of EGFR, IGF1R and detected α and β integrin determinants dropped dramatically. The degradation takes place in mid to late apoptosis. It was determined by real-time RT-PCR that the decrease in integrins, EGFR, IGF1R and MHC-1 determinants were not due to a reduction in transcription. Inhibitors of metallo­proteinases blocked the apoptotic decrease in cell surface determinants indicating that metalloproteinases mediated the reduction in these CDs in a manner that can reduce growth and survival signals while stimulating the NK surveillance system. Overall, the data indicate that the final stages of the pharmacological induction of apoptosis, while proceeding to a full commitment to non-necrotic cell death, involves the degradation of integrin, insulin and epidermal growth factor receptors caused by a programmed dysregulation of the cell's metalloproteinases.
View Figures
View References

Related Articles

Journal Cover

May-2014
Volume 44 Issue 5

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Magro A, Magro A, Shrestha S, Brundage K and Rankin G: Metalloproteinase dependent reduction of cell surface cluster determinants upon the induction of apoptosis. Int J Oncol 44: 1539-1550, 2014
APA
Magro, A., Magro, A., Shrestha, S., Brundage, K., & Rankin, G. (2014). Metalloproteinase dependent reduction of cell surface cluster determinants upon the induction of apoptosis. International Journal of Oncology, 44, 1539-1550. https://doi.org/10.3892/ijo.2014.2344
MLA
Magro, A., Magro, A., Shrestha, S., Brundage, K., Rankin, G."Metalloproteinase dependent reduction of cell surface cluster determinants upon the induction of apoptosis". International Journal of Oncology 44.5 (2014): 1539-1550.
Chicago
Magro, A., Magro, A., Shrestha, S., Brundage, K., Rankin, G."Metalloproteinase dependent reduction of cell surface cluster determinants upon the induction of apoptosis". International Journal of Oncology 44, no. 5 (2014): 1539-1550. https://doi.org/10.3892/ijo.2014.2344