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| Invited Talk, Saturday, 10:30 – 11:00 |
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| Cancer Cells regulate Biomechanical
Properties of Human Microvascular Endothelial Cells
Claudia Tanja Mierke
Soft Matter Physics Division, Institute
of Experimental Physics I, University of Leipzig, Linnéstraße
5, 04103 Leipzig, Germany |
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| Contact:
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Metastasis is a key event of malignant tumor progression. The capability
of tumors to metastasize depends on the cancer cell`s ability to migrate
into connective tissue, adhere, and possibly transmigrate through the endothelium.
Previously, we reported that the endothelium does not generally act as
barrier for cancer cells to migrate in 3D extracellular matrices (3D-ECMs).
Moreover, the endothelium acted as an enhancer or promoter for the invasiveness
of certain cancer cells. How invasive cancer cells diminished the endothelial
barrier function remains still elusive. Therefore, this study investigated
whether invasive cancer cells can decrease the endothelial barrier function
through alteration of endothelial biomechanical properties. To address
this, MDA-MB-231 breast cancer cells were used. They invaded deeper and
more numerous into 3D-ECMs when co-cultured with microvascular endothelial
cells. Using magnetic tweezer measurements MDA-MB-231 cells were found
to alter mechanical properties of endothelial cells by reducing their stiffness.
Using spontaneous bead diffusion actin cytoskeletal remodeling dynamics
were shown to be increased in co-cultured compared to mono-cultured endothelial
cells. In addition, knock-down of the alpha5 integrin subunit in highly-transmigrating
alpha5beta1high cells abolished the endothelial invasion enhancing effect
comparable to the inhibition of myosin light chain kinase indicating that
the endothelial invasion enhancing effect is alpha5beta1 integrin dependent.
In conclusion, decreased stiffness and increased cytoskeletal remodeling
dynamics of endothelial cells can explain the break-down of endothelial
barrier function indicating that biomechanical alterations were sufficient
to facilitate transmigration and invasion of invasive cancer cells into
3D-ECMs. |
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