Study Finds Tumor-Derived Exosomes May Predict Patients Likely to Develop Cancer Metastasis
Researchers investigating the role of exosomes, comprised of tumor-derived proteins, in the development of cancer metastasis have found that an “exosomal protein signature” could identify patients at risk for metastasis. The research also indicates that integrin expression profiles of circulating plasma exosomes isolated from patients with cancer could be used as prognostic factors to predict where the cancer is likely to spread. The study findings could provide oncologists with a method to predict organ-specific metastasis and help them tailor therapies to halt cancer spread. The study by Hoshino et al is published in Nature.
Study Methodology
The researchers used human breast cancer cell lines that spread to the lungs and human pancreatic cancer cell lines that spread to the liver. They then coupled a fluorescent dye to the fatty membranes of exosomes isolated from each cancer and injected them into healthy mice.
The investigators observed the exosomes traveling to and fusing with cells in the lungs and in the liver, respectively. They used the same approach to study 28 other cancers, including colorectal, lung, melanoma, and pediatric cancers that metastasize to specific organs, such as the lung, liver, and brain.
Study Findings
Using mass spectroscopy to analyze the proteins in the exosomes isolated from the cancer cell models, the researchers found that exosomal integrins—a family of binding proteins—direct organ-specific colonization by fusing with target cells in a tissue-specific fashion, thereby initiating premetastatic niche formation. For example, exosomes bearing alpha-6beta-4 and alpha-6beta-1 integrin promoted lung metastasis; alpha-vbeta-5 integrin promoted liver metastasis; and alpha-vbeta-3 integrin-expressing exosomes were associated with brain metastasis.
In addition, the researchers discovered that tumor-secreted exosomes are sufficient to redirect metastasis of tumor cells that normally lack the capacity to metastasize to a specific organ.
Predicting Metastasis
This study indicates that integrin-expression profiles of circulating plasma exosomes isolated from patients with cancer could be used as a prognostic tool to predict sites of future metastasis and provide a way to tailor treatment to stop metastatic spread.
“The integrin-specific signature that we identified may have significant value clinically, serving as a prognostic indictor for metastasis to specific organ sites,” said David C. Lyden, MD, PhD, the Stavros S. Niarchos Professor in Pediatric Cardiology and Associate Professor of Cell and Developmental Biology at Weill Cornell Medicine in New York, and senior author of this study, in a statement. “This will greatly assist clinicians in initiating preventive therapies for patients susceptible to developing organ-specific metastases.”
Dr. Lyden of Weill Cornell Medicine is a corresponding author of this study.
This study was supported by grants from the National Cancer Institute, National Institutes of Health, U.S. Department of Defense, and Melanoma Research Alliance, among others. The study authors declared no conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
