Pancreatic cancer exosomes may promote liver metastasis

Last Updated: 2015-05-28

By David Douglas

NEW YORK (Reuters Health) - Exosomes from pancreatic ductal adenocarcinomas contribute to a liver microenvironment conducive to cancer metastasis, according to researchers.

"Even prior to a recognizable pancreatic cancer, we discovered that pancreatic cells secrete microvesicles known as exosomes, which enter the circulation and fuse specifically with (Kupffer) cells in the liver," Dr. David C. Lyden told Reuters Health by email.

The Kupffer cells "then initiate a cascade of events promoting liver fibrosis and the pre-metastatic environment favorable for liver metastasis," he said. "We have confirmed that preparation for cancer metastasis begins as an early process rather than occurring as a late event as previously thought."

In a May 18 online paper in Nature Cell Biology, Dr. Lyden, of Weill Medical College of Cornell University, New York City, and colleagues noted that pancreatic ductal adenocarcinomas (PDACs) are highly metastatic with poor prognosis. Median survival is only about six months.

To help elucidate the underlying process, the investigators recreated the environment for pancreatic cancer in mice and discovered that exosomes found their way to the liver during the cancer's earliest stages.

The team also found that pancreatic cancer exosomes contain a protein called macrophage migration inhibitory factor (MIF). Eliminating MIF from the exosomes prevented the creation of a fibrotic, tumor-supporting environment in the liver.

Further work showed that stage I PDAC patients who later developed liver metastasis had markedly higher MIF levels in exosomes compared with patients whose pancreatic tumors did not progress.

"By obtaining a blood sample known as a liquid biopsy, we can detect cancer-related exosomes to predict cancer progression and metastasis to the liver," Dr. Lyden said.

"Exosomes and their protein packages can be useful as a biomarker to predict future metastasis, not only for the patients with pancreatic cancer, but also in patients with pre-tumoral lesions, such as those with pancreatitis," he said.

Ultimately, concluded Dr. Lyden, "By identifying the cascade of events in preparation of liver metastasis initiated by pancreatic cancer exosomes, then a multitargeted approach blocking each step can be applied in preventing or treating liver metastasis."

The authors reported no disclosures.

SOURCE: http://bit.ly/1dAcFVQ

Nature Cell Biol 2015.