Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study discovers how pancreatic cancer spreads to the liver

19.05.2015

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 The personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft

nachricht Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

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: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Fraunhofer ISE Pushes World Record for Multicrystalline Silicon Solar Cells to 22.3 Percent

25.09.2017 | Power and Electrical Engineering

Usher syndrome: Gene therapy restores hearing and balance

25.09.2017 | Health and Medicine

An international team of physicists a coherent amplification effect in laser excited dielectrics

25.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>