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Shining a Spotlight on Tumor Exosomes

David Lyden, M.D., Ph.D.

Stavros S. Niarchos Chair, Weill Cornell Medical College

Pediatric Neuro-Oncologist, Memorial Sloan Kettering Cancer Center

Metastasis causes about 90% of deaths from cancer. Understanding how cancer spreads throughout the body could reveal new opportunities to curtail tumor growth and help prolong the lives of cancer patients. Pediatric neuro-oncologist and researcher David Lyden is an NCI-funded scientist who has worked arduously for nearly two decades to uncover the steps of cancer cell metastasis.

David’s research focuses on exosomes, tiny sac-like structures, or vesicles, that are secreted by cells and circulate in the blood. Until recently, researchers had largely ignored exosomes and believed that tumor cells alone initiate metastasis at distant sites. However, David and his team discovered that, long before cancer cells arrive at a distant site, tumor exosomes help create a nurturing, or conditioned, environment for metastatic tumor growth. Through this and other work, they demonstrated that a primary tumor actively prepares so-called premetastatic niches in the body.

An unanswered question in metastasis research is why certain cancers preferentially metastasize to specific sites. For example, lung cancers often spread to the brain, and prostate cancers regularly spread to the bones. Expanding on their previous findings, David’s team made a discovery that sheds light on these patterns. “We saw that integrins, specific proteins on the surface of exosomes, direct where the exosomes will travel in the body,” he said. “We think of them as a molecular zip code.”

For example, one exosome might have integrins on its surface that bind to specific cells in the liver, thereby mediating metastasis to the liver, whereas another exosome might have integrins on its surface that bind to cells in the lungs, thus facilitating lung metastasis. Once the exosomes have reached their destination, they initiate local changes that help support the growth of future tumors.

This pioneering work—discovering the premetastatic niche and demonstrating the critical role of tumor exosomes—has ignited a new field of research. The number of scientists studying tumor exosomes has swelled from several dozen in 2012 to more than a thousand in 2017. They are increasing our understanding of exosome biology and hope to use this information to develop new ways to detect and treat cancer.

David is very passionate about the future of exosome research and is adamant that the goal of biological studies should be to help patients. “This research could help physicians identify patients whose tumors are not likely to metastasize, and thus help them avoid unnecessary treatment.” He thinks it could be possible to identify sites of future metastasis by tagging exosomes from a patient’s tumor and following them with imaging technologies. Furthermore, he wonders if blocking tumor exosome production may lead to better patient outcomes and fewer deaths due to metastasis.

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