Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Study discovers how pancreatic cancer spreads to the liver


An international team led by Weill Cornell Medical College investigators has illuminated the precise molecular steps that enable pancreatic cancer to spread to the liver -- the event that makes the most common form of the disease lethal. By understanding this process, investigators say their discovery can lead to targeted treatments that delay metastasis, and could offer clinicians a new biomarker to test for the earliest signs of pancreatic cancer.

The study, published May 18 in Nature Cell Biology, focuses on the role of small, spherical tumor-secreted packages, called exosomes, which contain tumor-derived proteins, in preparing a liver microenvironment fertile for pancreatic cancer metastasis.

This infographic illustrates the precise molecular steps that enable pancreatic cancer to spread to the liver.

Credit: Weill Cornell Medical College

Nearly 49,000 people in the United States will be diagnosed with pancreatic cancer, and more than 40,000 of them will succumb to it, according to estimates from the American Cancer Society. Pancreatic cancers are among the most lethal cancers -- only six percent of patients survive five years after diagnosis, with the median survival rate being just six months.

"What makes this cancer so lethal is that patients don't generally become symptomatic -- and as such aren't diagnosed -- until the cancer is very advanced and treatment options are limited," said senior author Dr. David Lyden, the Stavros S. Niarchos Professor in Pediatric Cardiology and a professor of pediatrics in the Department of Pediatrics at Weill Cornell Medical College.

In the study, the investigators recreated the environment for pancreatic cancer using mouse models and discovered that exosomes were finding their way to the liver during the cancer's earliest stages. Once in the liver, the exosomes were taken up by resident immune cells, called Kupffer cells. This process changed the Kupffer cells' gene expression and protein composition, and educated them to produce a powerful protein. This protein, in turn, affected the behavior of a group of cells, inducing liver fibrosis. Liver fibrosis is an overly exuberant wound healing process that can interfere with normal liver function, and creates a microenvironment auspicious for tumor seeding and growth.

When investigating how exosomes exerted these effects on liver cells, Dr. Lyden and his team found that pancreatic cancer exosomes contain a protein called macrophage migration inhibitory factor (MIF). When the investigators eliminated MIF from exosomes, they noticed that they had prevented the creation of a fibrotic, tumor-supporting environment in the liver.

"In mouse models of pancreatic cancer progression, exosomes containing MIF are released in circulation prior to the onset of a recognized pancreatic carcinoma and can 'educate' the liver, inducing fibrosis," said first authorDr. Bruno Costa Silva, an instructor of cell and developmental biology in pediatrics at Weill Cornell. "Our findings suggest that a microenvironment ripe for metastasis is generated at an earlier stage of the disease than previously recognized."

Once they understood this process, the investigators attempted to block each individual step in this sequence. "Disrupting just one part of the process at any point of the circuit decreased metastasis, a discovery that could lead to the development of multi-targeted therapies that could prolong patients' lives," said Dr. Lyden, who also has appointments in the Sandra and Edward Meyer Cancer Center and the Gale and Ira Drukier Institute for Children's Health. Dr. Lyden and his team conduct their research in the Children's Cancer and Blood Foundation labs at Weill Cornell.

Dr. Lyden and his team also found that MIF is highly expressed in exosomes circulating in patients who have advanced pancreatic cancer. When they examined pancreatic cancer blood samples, the scientists discovered that exosomal MIF was much higher in patients who went on to develop liver metastasis than in those who escaped it. They say this protein signature could be used to predict which patients would then go on to develop liver metastatic disease. These discoveries were made possible by an international collaboration between researchers at Weill Cornell Medical College, Memorial Sloan Kettering Cancer Center, University of Nebraska Medical Center, University of Pennsylvania and Oslo University Hospital.

Since five percent of patients diagnosed with pancreatitis -- a disease characterized by inflammation -- go on to develop pancreatic cancer, the investigators believe MIF could also serve as a biomarker for clinicians to monitor disease progression. Dr. Lyden and his team are currently testing whether measuring MIF levels in exosomes isolated from patients' blood can accurately estimate the risk of pancreatic cancer in patients with non-malignant pancreatic lesions. This type of "liquid biopsy" could allow the clinicians to initiate treatments, such as surgical resection, earlier in patients at risk, preventing disease progression.

Jen Gundersen | EurekAlert!

More articles from Studies and Analyses:

nachricht Diagnoses: When Are Several Opinions Better Than One?
19.07.2016 | Max-Planck-Institut für Bildungsforschung

nachricht High in calories and low in nutrients when adolescents share pictures of food online
07.04.2016 | University of Gothenburg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>