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.
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