angiogenesis
Using MicroRNA to Starve a Tumor?
Posted on by Dr. Francis Collins
Tumor cells thrive by exploiting the willingness of normal cells in their neighborhood to act as accomplices. One of their sneakier stunts involves tricking the body into helping them form new blood vessels. This growth-enabling process of sprouting new blood vessels, called tumor angiogenesis, remains a vital area of cancer research and continues to yield important clues into how to beat this deadly disease.
The two-panel image above shows one such promising lead from recent lab studies with endothelial cells, specialized cells that line the inside of all blood vessels. In tumors, endothelial cells are induced to issue non-stop SOS signals that falsely alert the body to dispatch needed materials to rescue these cells. The endothelial cells then use the help to replicate and sprout new blood vessels.
The left panel demonstrates the basics of this growth process under normal conditions. Endothelial cells (red and blue) were cultured under special conditions that help them grow in the lab. When given the right cues, those cells sprout spiky extensions to form new vessels.
But in the right panel, the cells can’t sprout. The reason is because the cells are bathed in a molecule called miR-30c, which isn’t visible in the photo. These specialized microRNA molecules—and humans make a few thousand different versions of them—control protein production by binding to and disabling longer RNA templates, called messenger RNA.
This new anti-angiogenic lead, published in the Journal of Clinical Investigation, comes from a research team led by Andrew Dudley, University of Virginia Medical School, Charlottesville [1]. The team made its discovery while studying a protein called TGF-beta that tumors like to exploit to fuel their growth.
Their studies in mice showed that loss of TGF-beta signals in endothelial cells blocked the growth of new blood vessels and thus tumors. Further study showed that those effects were due in part to elevated levels of miR-30c. The two interact in endothelial cells as part of a previously unrecognized signaling pathway that coordinates the growth of new blood vessels in tumors.
Dudley’s team went on to show that levels of miR-30c vary widely amongst endothelial cells, even when those cells come from the very same tumor. Cells rich in miR-30c struggled to sprout new vessels, while those with less of this microRNA grew new vessels with ease.
Intriguingly, they found that levels of this microRNA also predicted the outcomes for patients with breast cancer. Those whose cancers had high levels of the vessel-stunting miR-30c fared better than those with lower miR-30c levels. While more research is needed, it does offer a potentially promising new lead in the fight against cancer.
Reference:
[1] Endothelial miR-30c suppresses tumor growth via inhibition of TGF-β-induced Serpine1. McCann JV, Xiao L, Kim DJ, Khan OF, Kowalski PS, Anderson DG, Pecot CV, Azam SH, Parker JS, Tsai YS, Wolberg AS, Turner SD, Tatsumi K, Mackman N, Dudley AC. J Clin Invest. 2019 Mar 11;130:1654-1670.
Links:
Angiogenesis Inhibitors (National Cancer Institute/NIH)
Dudley Lab (University of Virginia School of Medicine, Charlottesville)
NIH Support: National Cancer Institute; National Heart, Lung, and Blood Institute
New Evidence Suggests Aging Brains Continue to Make New Neurons
Posted on by Dr. Francis Collins
Caption: Mammalian hippocampal tissue. Immunofluorescence microscopy showing neurons (blue) interacting with neural astrocytes (red) and oligodendrocytes (green).
Credit: Jonathan Cohen, Fields Lab, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH
There’s been considerable debate about whether the human brain has the capacity to make new neurons into adulthood. Now, a recently published study offers some compelling new evidence that’s the case. In fact, the latest findings suggest that a healthy person in his or her seventies may have about as many young neurons in a portion of the brain essential for learning and memory as a teenager does.
As reported in the journal Cell Stem Cell, researchers examined the brains of healthy people, aged 14 to 79, and found similar numbers of young neurons throughout adulthood [1]. Those young neurons persisted in older brains that showed other signs of decline, including a reduced ability to produce new blood vessels and form new neural connections. The researchers also found a smaller reserve of quiescent, or inactive, neural stem cells in a brain area known to support cognitive-emotional resilience, the ability to cope with and bounce back from stressful circumstances.
While more study is clearly needed, the findings suggest healthy elderly people may have more cognitive reserve than is commonly believed. However, the findings may also help to explain why even perfectly healthy older people often find it difficult to face new challenges, such as travel or even shopping at a different grocery store, that wouldn’t have fazed them earlier in life.
