Skip to main content
SpringerLink
Log in

AFM Observation of Heightened Cell Periphery of High-Grade Glioblastoma Cell Lines

  • Published:
BioNanoScience Aims and scope Submit manuscript

Abstract

Glioblastoma multiforme (GBM) is a highly invasive (WHO grade IV) brain tumour that has a very poor prognosis for patients with the condition (median survival 14.2 months). Quantitative Imaging (QI)® mode atomic force microscopy (AFM) was used to measure the heights of the leading-edge cell peripheries, the lamellipodia, of two such cell lines (SNB-19 and UP-007), together with those from non-neoplastic astrocyte control cells (CC-2565 and SC-1800) and from a low-grade (WHO grade I) glioma cell line (SEBTA-048). The lamellipodia heights of the glioma cells SNB-19 and UP-007 were 2.45 ± 0.59 and 1.57 ± 0.42 μm, respectively, which were higher than those of the CC-2565 and SC-1800 cells (1.03 ± 0.58 and 0.85 ± 0.40 μm, respectively; p < 0.0001, except between CC-2565 and UP-007, p < 0.001). Lamellipodia height differences between the two glioma cell lines (p < 0.0001) might be attributed to the measured difference in invasive potential between these two cell lines. The equivalent lamellipodia height of the SEBTA-048 cells was 1.16 ± 0.48 μm, the same as that of the astrocytes (p > 0.05) but lower than those of the high-grade gliomas (p < 0.0001 and p < 0.01 for SNB-19 and UP-007, respectively). These measured heights, therefore, may provide new insights for monitoring and controlling cellular invasion in brain tumours.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Louis, D. N., Ohgaki, H., Wiestler, O. D., Cavenee, W. K., Burger, P. C., Jouvet, A., et al. (2007). The 2007 WHO Classification of tumours of the central nervous system. Acta Neuropathologica, 114, 97–109. doi:10.1007/s00401-007-0243-4.

    Article  Google Scholar 

  2. Hoa, V. K. Y., Reijneveld, J. C., Enting, R. H., Bienfait, H. P., Robe, P., Baumert, B. G., et al. (2014). Changing incidence and improved survival of gliomas. European Journal of Cancer, 50, 2309–2318. doi:10.1016/j.ejca.2014.05.019.

    Article  Google Scholar 

  3. Cross, S. E., Jin, Y. S., Rao, J., Gimzewski, J. K. (2007). Nanomechanical analysis of cells from cancer patients. Nature Nanotechnology, 2, 780–783. doi:10.1038/nnano.2007.388.

    Article  Google Scholar 

  4. Docheva, D., Padula, D., Schieker, M., Clausen-Schaumann, H. (2010). Effect of collagen I and fibronectin on the adhesion, elasticity and cytoskeletal organization of prostate cancer cells. Biochemical and Biophysical Research Communications, 402, 361–366. doi:10.1016/j.bbrc.2010.10.034.

    Article  Google Scholar 

  5. Wang, B., Lancon, P., Bienvenu, C., Vierling, P., Di Giorgio, C., Bossis, G. (2013). A general approach for the microrheology of cancer cells by atomic force microscopy. Micron, 44, 287–297. doi:10.1016/j.micron.2012.07.006.

    Article  Google Scholar 

  6. Vadillo-Rodriguez, V., & Dutcher, J. R. (2009). Dynamic viscoelastic behavior of individual Gram-negative bacterial cells. Soft Matter, 5, 5012–5019. doi:10.1039/b912227c.

    Article  Google Scholar 

  7. Maherally, Z., Smith, J. R., An, Q., Pilkington, G. J. (2012). Receptors for hyaluronic acid and poliovirus: a combinatorial role in glioma invasion? PLoS One, 7, e30691. doi:10.1371/journal.pone.0030691.

    Article  Google Scholar 

  8. Maherally, Z., Smith, J. R., Ghoneim, M. K., Dickson, L., An, Q., Fillmore, H. L., Pilkington, G. J. (2015). Silencing of CD44 in glioma leads to changes in cytoskeletal protein expression and cellular biomechanical deformation properties as measured by AFM nanoindentation. BioNanoScience, 1–11. doi:10.1007/s12668-015-0189-2.

  9. Romet-Lemonne, G., & Jégou, A. (2013). Mechanotransduction down to individual actin filaments. European Journal of Cell Biology, 92, 333–338. doi:10.1016/j.ejcb.2013.10.011.

    Article  Google Scholar 

  10. Ridley, A. J. (2011). Life at the leading edge. Cell, 145, 1012–1022. doi:10.1016/j.cell.2011.06.010.

    Article  Google Scholar 

  11. Svitkina, T. M., & Borisy, G. G. (1999). Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in lamellipodia. Journal of Cell Biology, 145, 1009–1026. doi:10.1083/jcb.145.5.1009.

    Article  Google Scholar 

  12. Yamada, H., Ade, T., Li, S.-A., Masuoka, Y., Isoda, M., Watanabe, M., et al. (2015). Dynasore, a dynamic inhibitor, suppresses lamellipodia formation and cancer cell invasion by destabilizing actin filaments. Biochemical and Biophysical Research Communications, 390, 1142–1148. doi:10.1016/j.bbrc.2009.10.105.

    Article  Google Scholar 

  13. Chopinet, L., Formosa, C., Rols, M. P., Duval, R. E., Dague, E. (2013). Imaging living cells surface and quantifying its properties at high resolution using AFM in QI™ mode. Micron, 48, 26–33. doi:10.1016/j.micron.2013.02.003.

    Article  Google Scholar 

  14. An, Q., Fillmore, H. L., Vouri, M., Pilkington, G. J. (2014). Brain tumour cell line authentication, an efficient alternative to capillary electrophoresis by using a microfluidics-based system. Neurooncology, 16, 265–273. doi:10.1093/neuonc/not202.

    Google Scholar 

  15. Pilkington, G. J., Akinwunmi, J., Ognjenovic, N., Rogers, J. P. (1993). Differential binding of anti-CD44 on human gliomas in vitro. Neuroreport, 4, 259–262. doi:10.1097/00001756-199303000-00008.

    Article  Google Scholar 

  16. Hutter, J. L., & Bechhoefer, J. (1993). Calibration of atomic-force microscope tips. Review of Scientific Instruments, 64, 1868–1873. doi:10.1063/1.1143970.

    Article  Google Scholar 

  17. Fillmore, H. L., Chasiotis, I., Cho, S. W., Gillies, G. T. (2003). Atomic force microscopy observations of tumour cell invadopodia: novel cellular nanomorphologies on collagen substrates. Nanotechnology, 14, 73–76. doi:10.1088/0957-4484/14/1/317.

    Article  Google Scholar 

  18. Chasiotis, I., Fillmore, H. L., Gillies, G. T. (2003). Atomic force microscopy measurement of cytostructural elements involved in the nanodynamics of tumour cell invasion. Nanotechnology, 14, 557–561. doi:10.1088/0957-4484/14/5/314.

    Article  Google Scholar 

  19. D’Agostino, D. P., Olson, J. E., Dean, J. B. (2009). Acute hyperoxia increases lipid peroxidation and induces plasma membrane blebbing in human U87 glioblastoma cells. Neuroscience, 159, 1011–1022. doi:10.1016/j.neuroscience.2009.01.062.

    Article  Google Scholar 

  20. Selmeczi, D., Szabo, B., Sajo-Bohus, L., Rozlosnik, N. (2001). Morphological changes in living cell cultures following α-particle irradiation studied by optical and atomic force microscopy. Radiation Measurement, 34, 549–553. doi:10.1016/S1350-4487(01)00226-8.

    Article  Google Scholar 

  21. Bastatas, L., Martinez-Marin, D., Matthews, J., Hashem, J., Lee, Y. J., Sennoune, S., et al. (2012). AFM nano-mechanics and calcium dynamics of prostate cancer cells with distinct metastatic potential. Biochimica et Biophysica Acta, 1820, 1111–1120. doi:10.1016/j.bbagen.2012.02.006.

    Article  Google Scholar 

  22. Zhang, X., Tang, Q., Wu, L., Huang, J., Chen, Y. (2015). AFM visualization of cortical filaments/network under cell-bound membrane vesicles. Biochimica et Biophysica Acta, 1848, 2225–2232. doi:10.1016/j.bbamem.2015.06.025.

    Article  Google Scholar 

  23. Birukova, A. A., Arce, F. T., Moldobaeva, N., Dudek, S. M., Garcia, J. G. N., Lal, R., et al. (2009). Endothelial permeability is controlled by spatially defined cytoskeletal mechanics: atomic force microscopy force mapping of pulmonary endothelial monolayer. Nanomedicine: Nanotechnology, Biology and Medicine, 5, 30–41. doi:10.1016/j.nano.2008.07.002.

    Article  Google Scholar 

Download references

Acknowledgments

We thank Drs. Robert Field and Alex Winkle from JPK Instruments, Cambridge, UK, for loan of the NanoWizard 3 AFM instrument, and Brain Tumour Research for support. We also thank Prof. Keyoumars Ashkan and Dr. Stavros Polyzoidis, of the Department of Neurosurgery, King’s College Hospital, London, UK, for providing the brain tumour biopsy sample for establishment as a primary cell line (SEBTA-048).

Author information

Authors and Affiliations

  1. Cellular and Molecular Neuro-oncology Research Group, School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael’s Building, White Swan Road, Portsmouth, PO1 2DT, UK

    James R. Smith, Zaynah Maherally, Samantha C. Higgins, Qian An, Helen L. Fillmore & Geoffrey J. Pilkington

Authors
  1. James R. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zaynah Maherally
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Samantha C. Higgins
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qian An
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Helen L. Fillmore
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Geoffrey J. Pilkington
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James R. Smith.

Ethics declarations

Ethics Statement

All cell lines established in-house were conducted in accordance with the National Research Ethics Service (NRES) instructions and under ethics permission 11/SC/0048.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Smith, J.R., Maherally, Z., Higgins, S.C. et al. AFM Observation of Heightened Cell Periphery of High-Grade Glioblastoma Cell Lines. BioNanoSci. 6, 47–53 (2016). https://doi.org/10.1007/s12668-015-0188-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12668-015-0188-3

Keywords

Search

Navigation