We know that cells are constantly secreting molecules that can have many different biological impacts; the term extracellular vesicle is used to refer to a group of little membrane-enclosed sacs that most cells release. Scientists have also identified exomeres, particles cells release that are not bound by a membrane. Now, even smaller particles have been found within those exomeres. These nanoparticles are full of bioactive chemicals, including enzymes, proteins, and RNA molecules that have been linked to diseases including cardiovascular disease, Alzheimer's, and several types of cancer. The researchers have called these nanoparticles 'supermeres.' The findings have been reported in Nature Cell Biology, and could help us learn more about how particles that are released by cells are involved in cell signaling, health, and disease.
“We’ve identified a number of biomarkers and therapeutic targets in cancer and potentially in a number of other disease states that are cargo in these supermeres,” said senior study author, Robert Coffey, MD, the Ingram Professor of Cancer Research and professor of Medicine and Cell & Developmental Biology at Vanderbilt University Medical Center. “What is left to do now is to figure out how these things get released.”
Scientists in the Coffey lab have been studying nanoparticles that are linked to cancer, and whether they can inform detection or aid treatment. Various parts of cells can be separated using centrifugation; particles of different densities can be located based on their position in a centrifugation tube after a spin.
Study co-author Qin Zhang, PhD, a research assistant professor of Medicine at Vanderbilt, used high-speed ultracentrifugation to isolate exomeres. Zhang spun the exomeres down further, and removed the leftover fluid or supernatant for analysis. Supermeres were found in that supernatant.
“They’re also super interesting because they contain many cargo previously thought to be in exosomes,” said Coffey. That cargo apparently includes the majority of extracellular RNA that cells release, and some disease-related proteins.
Supermeres that come from cancer cells can carry drug resistance to other tumor cells, and that process may be facilitated by RNA. Some proteins carried by supermeres include TGFBI, which promotes tumor progression in growing tumors. Another is ACE2, a receptor well-known for giving SARS-CoV-2 entry to cells, but which has also been linked to cardiovascular disease.
Supermeres were also found to contain a protein that may be involved in the development of Alzheimer's, called APP (amyloid-beta precursor protein). Supermeres seem to be able to penetrate the blood-brain barrier, so they might be useful in the detection of a variety of disorders.