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Archive - Oct 26, 2015

Astrocyte-Derived Exosomal miRNA Induces Loss of PTEN Gene Expression in Brain & Primes Brain Tumor Metastasis; More Evidence for Dynamic and Reciprocal Cross-Talk Between Tumor Cells and Metastatic Environment

It’s no surprise that people enjoy warm places like Hawaii, but may suffer in hostile locales such as Antarctica. A tumor suppressor gene called PTEN is similar in that it is affected by the microenvironments of certain bodily organs in which it finds itself. Scientists at The University of Texas MD Anderson Cancer Center, together with colleagues, have found that PTEN is regulated by different organs. For patients with brain metastases, this is not good, as PTEN in cells is shut off in the brain. Surprisingly, PTEN is restored once cells migrate to other organs. It’s a discovery that may be important for developing effective new anti-metastasis therapies of particular importance for advanced-stage brain cancer patients. The study findings were published in the October 19, 2015 issue of Nature. The article is titled “Microenvironment-Induced PTEN Loss by Exosomal microRNA Primes Brain Metastasis Outgrowth.” “Development of life-threatening cancer metastasis requires that tumor cells adapt to and evolve within drastically different microenvironments of metastatic sites,” said Dihua Yu (photo), M.D., Ph.D., Deputy Chair of the Department of Molecular and Cellular Oncology at MD Anderson. “Yet it is unclear when and how tumor cells acquire the essential traits in a foreign organ’s microenvironment that lead to successful metastasis. Our study showed that primary tumor cells with normal PTEN expression lose PTEN expression when they reach the brain, but not in other organs.” The study of Dr. Yu and colleagues found that metastatic brain tumor cells that have experienced PTEN loss have PTEN levels restored once they leave the brain. The researchers determined that the “reversible” PTEN loss is induced by microRNAs (miRNAs) from astrocytes located in the brain and spinal cord.

Exosomes from Stem Cell Transplants Transfer Normal Fas Protein in Mouse Model of Systemic Lupus Erythematosus (SLE); May Underly Mechanism for Mysterious Bone Preservation Induced by Such Transplants

People with lupus, an autoimmune disease, suffer from fatigue, joint pain, and swelling, and also have a markedly increased risk of developing osteoporosis. Clinical trials have shown that receiving a mesenchymal stem cell transplant (MSCT) can greatly improve the condition of lupus patients, yet it has not been clear why this treatment strategy works so well. Now, University of Pennsylvania (Penn) researchers, and colleagues, have puzzled out a mechanism by which stem cell transplants may help preserve bone in an animal model of lupus. In a paper published in the October 6, 2015 issue of Cell Metabolism, the research team shows that the transplanted cells provide a source (exosomes) of a key protein called Fas, which improves the function of bone marrow stem cells through a multi-step, epigenetic effect. The work has implications for potential therapeutic strategies for lupus, as well as other diseases for which stem cell transplants have shown promise. “When we used stem cells for these diseases and put them into the circulation, we didn’t know exactly what they were doing, but saw that they were very effective,” said Songtao Shi (photo), D.D.S., Ph.D., Chair and Professor of the Department of Anatomy and Cell Biology in Penn’s School of Dental Medicine and a co-corresponding author on the paper. “Now we’ve seen, in a model of lupus, that bone-forming mesenchymal stem cell function was rescued by a mechanism that was totally unexpected.” Dr. Shi collaborated on the work with Shiyu Liu, Dawei Liu, Chider Chen, and Ruili Yang of Penn Dental Medicine; Kazunori Hamamura, Alireza Moshaverinia, and Yao Liu of the University of Southern California; and co-corresponding author Yan Jin of China’s Fourth Military Medical University.

Siberian Jays Can Recognize Unfamiliar, Distant Relatives

Can animals recognize distantly related, unfamiliar individuals of the same species? Evolutionary biologists from the University of Zurich have demonstrated, for the first time, that Siberian jays (image) possess this somewhat amazing ability. The new findings were published online on October 13, 2015 in Molecular Ecology. The article is titled “Fine-Scale Kin Recognition in the Absence of Social Cues in the Siberian Jay, a Monogamous Bird Species.” Siberian jays belong to the crow family and the new work shows that they are able to accurately assess the degree of kinship to unfamiliar individuals. This ability confers advantages when sharing food and other forms of cooperation. In a few mammal, bird, and fish species, it is known that individuals can recognize unfamiliar siblings. Until now, however, it remained unclear whether animals are also able to identify more distant, unfamiliar relatives. The new work has now shown that Siberian jays evolved this ability. Kinship is a critical factor favoring cooperation between and among individuals. The reason behind this is likely that helping closely related individuals aids in propagating one’s own genes. Consequently, most insects, meerkats, or birds that breed cooperatively (i.e., individuals help to raise offspring that are not their own) live in family groups. The Siberian jay, which occurs in Northern Scandinavia and the Siberian taiga lives in family groups that share a territory. Non-breeding birds are both offspring that remain with their parents for several year beyond independency and individuals that immigrate into groups early in their lives. [Note: The Siberian taiga, also known as boreal forest or snow forest, is a biome characterized by coniferous forests consisting mostly of pines, spruces, and larches.