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Human Endothelial Cells as Barriers

Endothelial Cells as Blood Vessel Barriers — The Latest Research Studies

Endothelial cells form a monolayer that lines the lumen of blood vessels, provides an essential protective barrier, and regulates vessel and blood pressure homeostasis. Endothelial cells are also involved in forming new blood vessels, a process called angiogenesis. During cancer cell metastasis, cancer cells break off from a primary tumor and travel through the bloodstream to establish a new tumor in a distant site. To do this, cancer cells must exit the bloodstream and enter the new tissue, a process called extravasation. Extravasation requires cancer cells to travel through the endothelial cell layer; therefore, endothelial cells also serve as an important barrier to metastasis.

Recent Studies Using Lifeline® Endothelial Cells: Autophagy and Extravasation

Autophagy is the process by which cells degrade and recycle cellular organelles that may be damaged, or whose components may be needed in starvation conditions. In a 2014 study, Goyal and colleagues investigated the signaling pathways that mediate autophagy downstream of decorin, an extracellular matrix protein that negatively regulates receptor tyrosine kinase signaling. This work follows up on a previous study by this group that established a role for decorin in autophagy through vascular endothelial growth factor receptor (VEGFR2). In the current study, the group used Lifeline® human umbilical vein endothelial cells (HUVECs) to perform their studies. They first established that decorin-mediated autophagy is dependent on the kinase Vps34, which binds Beclin 1 (an important autophagy protein) and this association in turn initiates autophagy. Furthermore, the researchers found that decorin induced downregulation of the Akt/mTOR pathway, which negatively regulates autophagy. Finally, the group discovered that decorin activates AMPK (a kinase that regulates cellular energy) through VEGFR2, a stimulus that serves to induce autophagy. Together, the results of this study illuminate a pathway from decorin and VEGFR2 on the cell surface, to AMPK activation and Akt/mTOR inactivation inside the cells, resulting in endothelial autophagy.

Cancer cell metastasis from a primary tumor to a distant site is the main cause of cancer-related death and one of the biggest challenges for cancer therapy. In a 2014 study, Hamilla et al. examined the dynamics of cancer cell extravasation through a monolayer of Lifeline® HUVECs. They found that metastatic MDA-MB-231 breast cancer cells displaced individual endothelial cells to incorporate into the monolayer. A375 and SW1990 melanoma and pancreatic cancer cells, respectively, behaved similarly, while neutrophils transversed the endothelial monolayer without disrupting it. Furthermore, the group found that the incorporation of MDA-MB-231 or A375 cells into the endothelial cell layer was not changed upon activation of endothelial cells by tumor necrosis factor alpha (TNF-a), or by the stiffness of the substrate underlying the endothelial cell layer. SW1990 cells did have increased incorporation upon endothelial activation, suggesting that this behavior may be context-dependent for certain cancer cells. Finally, the researchers examined the expression of vascular endothelial cadherin (VE-cadherin), which is expressed at cell-cell junctions of confluent endothelial cells. Interestingly, they found that where MDA-MB-231 cells incorporated into the endothelial monolayer, VE-cadherin-positive junctions were disrupted, creating a larger space for the cancer cell to break through the monolayer. Together, the results from this study suggest that metastatic cancer cells incorporate into endothelial monolayers during early extravasation, disrupting VE-cadherin-positive cell-cell junctions and resultant endothelial integrity.

Lifeline® endothelial cell types

Let us know how you are using Lifeline® endothelial cells and VascuLife® Optimized Cell Culture Media. Your study could be featured here on our blog!

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