Cancer cells impact the microrheology of endothelial cells during physical contact or through paracrine signalling

被引:0
作者
Kefala, Georgia M. [1 ,2 ]
Tsvirkun, Daria [1 ]
Laurent, Valerie M. [1 ]
Verdier, Claude [1 ]
机构
[1] Univ Grenoble Alpes, CNRS, LIPhy, F-38000 Grenoble, France
[2] LEIDEN UNIV, POB 9500, NL-2300 RA LEIDEN, Netherlands
来源
SCIENTIFIC REPORTS | 2025年 / 15卷 / 01期
关键词
AFM; Cancer; Viscoelastic; Endothelium; T24; cells; TRANSENDOTHELIAL MIGRATION; BIOMECHANICAL PROPERTIES; MELANOMA-CELLS; EXTRAVASATION; TRANSMIGRATION; ACTIVATION; DYNAMICS;
D O I
10.1038/s41598-025-92422-w
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
During the process of metastasis, cancer cells transmigrate through the endothelial barrier of the vascular walls. Cancer cells interact with the endothelial cells, leading to changes of their mechanical properties. While this interaction has been extensively studied from the perspective of cancer cells (CCs), the mechanical properties of the endothelium remain underexplored, even though they may play a crucial role in regulating this process. In this study, we used a microrheology AFM-based approach to demonstrate that the properties of endothelial cells (ECs) are altered when cultured either in CC-conditioned medium or in direct contact with cancer cells. We found that the viscoelasticity of ECs decreased when cultured in diluted CC-conditioned medium. Furthermore, ECs in direct contact with a cancer cell at short times (less than 30 min) also showed significantly lower stiffness and viscoelastic moduli. In parallel, we observed a reduction in the quantity of actin fibers and actin clusters within the EC cytoskeleton, resulting in a less structured network that may facilitate CC transmigration. Overall, our findings indicated that the rheological properties of ECs can be altered either directly through physical contact with CCs or indirectly via CC-secreted substances. This suggests that the endothelium actively responds to the presence of cancer cells, rather than serving only as a passive barrier.
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页数:12
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共 68 条
  • [21] Chen M.B., Whisler J.A., Jeon J.S., Kamm R.D., Mechanisms of tumor cell extravasation in an in vitro microvascular network platform, Integr. Biol, 5, pp. 1262-1271, (2013)
  • [22] Jeon J.S., Zervantonakis I.K., Chung S., Kamm R.D., Charest J.L., In vitro model of tumor cell extravasation, PLoS ONE, 8, (2013)
  • [23] Aragon-Sanabria V., Et al., VE-cadherin disassembly and cell contractility in the endothelium are necessary for barrier disruption induced by tumor cells, Sci. Rep, 7, (2017)
  • [24] Brock T., Et al., The influence of VE-cadherin on adhesion and incorporation of breast cancer cells into vascular endothelium, Int. J. Mol. Sci, 22, (2021)
  • [25] Qi J., Chen N., Wang J., Siu C.-H., Transendothelial migration of melanoma cells involves N-cadherin-mediated adhesion and activation of the beta-catenin signaling pathway, Mol. Biol. Cell, 16, pp. 4386-4397, (2005)
  • [26] Weidert E., Pohler S.E., Gomez E.W., Dong C., Actinomyosin contraction, phosphorylation of VE-cadherin, and actin remodeling enable melanoma-induced endothelial cell-cell junction disassembly, PLoS ONE, 9, (2014)
  • [27] Grady M.E., Composto R.J., Eckmann D.M., Cell elasticity with altered cytoskeletal architectures across multiple cell types, J. Mech. Behav. Biomed. Mater, 61, pp. 197-207, (2016)
  • [28] Xie L., Et al., Changes in dynamics of tumor/endothelial cell adhesive interactions depending on endothelial cell growth state and elastic properties, PLoS ONE, 17, (2022)
  • [29] Wang L., Tian L., Zhang W., Wang Z., Liu X., Effect of AFM nanoindentation loading rate on the characterization of mechanical properties of vascular endothelial cel, Micromachines, 11, (2020)
  • [30] Starodubtseva M.N., Et al., Heterogeneity of nanomechanical properties of the human umbilical vein endothelial cell surface, Microvasc. Res, 136, (2021)