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Seminarium ACMiN: The dark side of the force - how alterations in tissue mechanics influence brain cancer development?
Czwartek, 23. Styczeń 2020, 14:00 - 16:00

Uprzejmie zapraszamy na Seminarium ACMiN, które odbędzie się w czwartek 23 stycznia 2020 r. o godz. 14.00 w Sali Audytoryjnej ACMiN AGH na II piętrze budynku D-16 (ul. Kawiory 30).

Referat pt. "The dark side of the force - how alterations in tissue mechanics influence brain cancer development?" wygłosi dr Katarzyna Pogoda (Institute of Nuclear Physics PAN, Krakow, Poland).

Streszczenie:

Glioblastomas (GBM) are diffuse and highly invasive tumors that originate in brain and make up about 50% of all primary brain and CNS tumors. Unlike solid tumors glioblastomas are characterized by high intratumor heterogeneity and consist of regions with multiple subpopulations of the cells with various extracellular matrix compositions that support development of resistance to radiation and chemotherapy. GBM possess unique soft matter properties, which discriminate them from other soft tissue-derived tumors with relatively low content of fibrous proteins even in high grade tumors. Moreover, the boundary between tumor and normal tissue is not sharp, and single glioma cells rapidly infiltrate different brain regions and proliferate, which leads to recurrence after surgical resection of the primary tumor (Pogoda & Janmey, 2018). For this reason, one of the central therapeutic goals is to limit cell migration and division, and thereby identify molecular regulators of GBM cell motility and proliferation in vitro and in vivo.

Although glioblastoma development is not accompanied by significant increase in stiffness, as is observed for breast or liver cancer when measured ex vivo, brain tissue can stiffen in compression. This compression-stiffening behavior might be sufficient to trigger the same mechanical response that is activated when single-cells are grown on substrates with different stiffness. Single glioma cells respond to substrate mechanics by increasing in proliferation, motility and invasiveness when cultured on a stiffer environments (Pogoda et al., 2014, 2017). Substrate stiffness can also regulate cellular uptake of nanoparticles and thus, glioma cells response to treatment (Pogoda et al., in preparation). Slow-growing brain tumors can also generate solid-stress that is exerted by surrounding brain tissue and results in neurological disfunction due to neuronal loss and limited vascular perfusion (Seano et al., 2019). But whether these solid stresses accelerate tumor growth or facilitate multiple brain metastases remains an open question (Janmey & Pogoda, 2019).

Bibliography

Janmey, P. A., & Pogoda, K. (2019). Compressive tumours cause neuronal damage. Nature Biomedical Engineering, 3(3), 171–172. https://doi.org/10.1038/s41551-019-0370-y

Pogoda, K., Bucki, R., Byfield, F. J., Cruz, K., Lee, T., Marcinkiewicz, C., & Janmey, P. A. (2017). Soft Substrates Containing Hyaluronan Mimic the Effects of Increased Stiffness on Morphology, Motility, and Proliferation of Glioma Cells. Biomacromolecules, 18(10), 3040–3051. https://doi.org/10.1021/acs.biomac.7b00324

Pogoda, K., Chin, L., Georges, P. C., Byfield, F. J., Bucki, R., Kim, R., … Janmey, P. A. (2014). Compression stiffening of brain and its effect on mechanosensing by glioma cells. New Journal of Physics, 16(7), 75002. https://doi.org/10.1088/1367-2630/16/7/075002

Pogoda, K., & Janmey, P. A. (2018). Glial Tissue Mechanics and Mechanosensing by Glial Cells. Frontiers in Cellular Neuroscience, 12, 25. https://doi.org/10.3389/fncel.2018.00025

Seano, G., Nia, H. T., Emblem, K. E., Datta, M., Ren, J., Krishnan, S., … Jain, R. K. (2019). Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium. Nature Biomedical Engineering, 3(3), 230–245. https://doi.org/10.1038/s41551-018-0334-7

Miejsce : Sala Audytoryjna ACMiN AGH (1.02A), na II piętrze pawilonu D-16 (ul. Kawiory 30).