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Fazakas Csilla

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Végh Attila Gergely
The force awakens: mechanical interaction of metastatic tumor cells with the neurovascular unit

Aug 30 - szerda

14:00 – 14:18

Sejtanalitika biofizikai megközelítéssel

E32

The force awakens: mechanical interaction of metastatic tumor cells with the neurovascular unit

Attila Gergely Végh¹, Katalin Csonti^1,2,3, Csilla Fazakas¹, Kinga Molnár¹, Imola Wilhelm^1,4 and István Krizbai^1,4

¹ Biological Research Centre, Szeged, Institute of Biophysics

² Doctoral School of Physics, University of Szeged

³ Semilab Semiconductor Physics Laboratory Co. Ltd., Budapest

⁴ Institute of Life Sciences, Vasile Goldis Western University, Arad

The central nervous system has prominent defense lines, however, most of the malignancies detected within the brain parenchyma are of metastatic origin. As the brain lacks classical lymphatic circulation, the primordial way for metastasis relies on hematogenous routes. The first and probably the most crucial step for invading tumor cells relies on their interaction with the neurovascular unit. The neurovascular unit plays crucial role in the maintenance of the proper homeostasis of the central nervous system [1]. Endothelial cells and pericytes are the most exposed to mechanical stresses their mechanobiology is of primordial importance [2]. Furthermore, tumor cell derived extracellular vesicles might play key role in pre-metastatic niche formation and might be involved in metastatic organotropism [3].

Single cell-force spectroscopy was applied to investigate the adhesive properties of living breast adenocarcinoma cells to confluent layers of brain endothelial cells and pericytes. Cell type dependent adhesion characteristics were found as well as the existence of metastatic potential related nanomechanical differences between the studied tumor cells, relying partly on membrane tether dynamics. Apparent mechanical properties such as elasticity, maximal adhesion force, number, size and distance of individual rupture events have been found cell type dependent, correlating with their metastatic abilities. Additionally, tumor cell derived extracellular vesicles alter the adhesive properties of tumor cells to brain endothelial layer. Exploring the mechanobiology of constituent of the neurovascular unit could not only lead to a better understanding of their function but could also help to identify novel targets for the improvement of its barrier function.

References

[1] J. Gállego Pérez-Larraya and J. Hildebrand, “Brain metastases,” Handb. Clin. Neurol., vol. 121, pp. 1143–1157, 2014, doi: 10.1016/B978-0-7020-4088-7.00077-8.

[2] I. Wilhelm, C. Fazakas, K. Molnár, A. G. Végh, J. Haskó, and I. A. Krizbai, “Foe or friend? Janus-faces of the neurovascular unit in the formation of brain metastases,” J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab., p. 271678X17732025, Jan. 2017, doi: 10.1177/0271678X17732025.

[3] Y. Guo et al., “Effects of exosomes on pre-metastatic niche formation in tumors,” Mol. Cancer, vol. 18, no. 1, p. 39, Mar. 2019, doi: 10.1186/s12943-019-0995-1.