Cancer Cells Alter Endothelial Cell Mechanics, Impacts on Metastasis Revealed
Recent research uncovers the dynamic relationship between cancer cells and endothelial cells, demonstrating how these interactions can significantly impact the process of metastasis.
The study, published on March 8, 2025, highlights the mechanical adaptations of endothelial cells (ECs) when exposed to cancer cells (CCs). Traditionally viewed as passive barriers, it appears ECs actively respond to the presence of CCs, altering their mechanical properties to facilitate cancer cell transmigration through the vascular endothelium.
The researchers employed atomic force microscopy (AFM)-based microrheology to assess the alterations in the rheological properties of ECs. They revealed compelling results demonstrating decreased stiffness and altered viscoelasticity when ECs were cultured either with cancer cell-conditioned medium or were directly exposed to the cancer cells themselves.
Specifically, endothelial cells cultured with CC-conditioned medium exhibited 1.3 kPa Young's modulus compared to 1.8 kPa for controls. The alterations were even more pronounced when ECs were directly contacted by cancer cells, measuring only 0.7 kPa. This suggests not only physical interactions but also biochemical signaling is at play.
According to the authors of the article, "Overall, our findings indicated...that the endothelium actively responds to the presence of cancer cells, rather than serving only as a passive barrier." This change was facilitated not only by direct contact but significantly through paracrine signaling from the CCs to the ECs.
Endothelial cell mechanics are now understood to be more complex than previously thought. The results indicate decreased actin fibers and clusters within the EC cytoskeleton—an outcome of interaction with CCs—which leads to less structural organization, thereby promoting cancer cell migration.
Further experiments found distinct rheological behaviors as the frequency of applied force oscillated across different experimental conditions. Endothelial cells were seen to transition from elastic to viscous states, underlining the complexity of cell mechanics within the vasculature influenced by tumors.
Prior findings primarily examined CC properties; this study shifts focus to elucidate how the endothelial side reacts—a promising avenue for future exploration and therapeutic strategies against metastasis.
Overall, the study emphasizes the necessity to explore treatments targeting these cellular interactions to effectively curb metastasis by restoring normal endothelial function. Researchers continue to highlight the importance of gaining insights from this complex interaction, paving the way for future cancer therapeutic strategies.