Blood vessels, the essential delivery system of molecules to all tissues, are covered with a special type of cells – endothelial cells (ECs). These not only facilitate the exchange of beneficial compounds but also actively support the passage of leukocytes (white blood cells) towards areas that signal an inflammatory response.
Inflammation is one of the hallmarks of cancer so ECs may actually play a more important role in disease evolution than previously thought.
In a recent study published in Developmental Cell, researchers from Osaka University examined the mechanism underlying endothelial cell resistance to TNFα-induced apoptosis, a key process that leads to cell death in inflammatory conditions. They found that a common signaling messenger involved in tissue homeostasis, TAK1, is crucial for ensuring the survival of endothelial cells during inflammation and injury.
“We found that deletion of TAK1 blocked the ability of intestinal endothelial cells to disregard monocyte and macrophage inflammatory TNFα signaling induced by intestinal microbiota, resulting in hemorrhage within the intestine and liver”, explained corresponding author Nobuyuki Takakura. “Thus, the presence of TAK1 safeguarded the survival of endothelial cells in these tissues”.
Besides providing a better understanding of how endothelial cells perform during inflammation, these findings also revealed a potential pathway for other cell types to avoid the onset of apoptosis, and may be important in future regenerative medicine therapies.
“We suspected that inflammation in tumor tissues may be a powerful weapon to destroy tumor vasculature”, noted lead author Hisamichi Naito. “We found that, in the tumor in which TNFα is expressed abundantly, localized deletion of TAK1 resulted in endothelial cell death and thereby tumor regression, suggesting that TAK1 may be a useful target in anti-angiogenic therapy”.
Using a targeted approach to basically cut off the energy supply for tumors without affecting nearby healthy tissue would result in safer treatments and also offer improved outcomes for patients battling cancer.
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