Asymmetric flow field-flow fractionation (AF4) was used by Weill Cornell Medicine scientists to separate two distinct exosome subpopulations (large exosome vesicles, Exo-L, and small exosome vesicles, Exo-S) and discover a new nanoparticle that they named “exomeres”. According to a paper published earlier this week in Nature Cell Biology, the discovery of this new cellular messenger may help reveal how cancer cells co-opt the body's intercellular delivery service to spread to new locations in the body.
"We found that exomeres are the most predominant particle secreted by cancer cells," said senior author David Lyden. "They are smaller and structurally and functionally distinct from exosomes. Exomeres largely fuse with cells in the bone marrow and liver, where they can alter immune function and metabolism of drugs. The latter finding may explain why many cancer patients are unable to tolerate even small doses of chemotherapy due to toxicity."
"Exosomes and exomeres also have different biophysical characteristics, such as stiffness and electric charge, that likely affect their behavior in the body," said lead author Haiying Zhang. "The more rigid the particle, the easier it is likely taken up by cells, rendering exomeres, which are stiffer than exosomes, the more effective messengers of transferring tumor information to recipient cells."
Exosomes and exomeres also differ in the way they influence cancer. Exomeres carry metabolic enzymes to the liver. The finding suggests that exomeres target the liver to "reprogram" its metabolic function to favor tumor progression. Exomeres also carry blood-clotting factors to the liver, where they may prohibit the liver's normal function in regulating clotting. By contrast, the study suggests that Exo-L may promote metastasis to lymph nodes, while Exo-S may support distant metastasis.
"Cancer is truly a systemic disease that requires multi-organ involvement to progress," Dr. Lyden emphasized. "Our finding that tumor cells secrete these three distinct nanoparticles, that then target cells in different organs reflects this important aspect of the disease."