The Society of Cancer Management
  • Home
    • An After Life
    • News Archive
  • About
    • Terms & Conditions
    • Privacy Policy
    • Copyright Notice
  • Contact

. . . supporting research that improves cancer survival.

 
Please contact us if you would like to contribute a news item. We are keen to publish more articles from UK-based research and findings that relate to microbial infections during therapy.

Study discovers how pancreatic cancer spreads to the liver

19/5/2015

0 Comments

 
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, 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.

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.

Picture
MIF-expressing pancreatic cancer exosomes induce/prepare liver metastasis. Pancreatic cancer exosomes induce liver fibrosis (fibronectin, green) and immune cells (macrophages, red) accumulate.
Image credit: Dr. Bruno Costa da Silva and Dr. David Lyden

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.


Costa-Silva et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nature Cell Biol. 2015; doi:10.1038/ncb3169 [Abstract]
0 Comments

Your comment will be posted after it is approved.


Leave a Reply.

    Cancer Therapy & Palliative Care News

    This feed features recent developments in cancer therapy and palliative care. Views in these articles do not necessarily represent those of the Cancer Management Society.

    Archives

    March 2021
    February 2021
    January 2021
    December 2020
    November 2020
    October 2020
    September 2020
    August 2020
    July 2020
    June 2020
    May 2020
    April 2020
    March 2020
    February 2020
    January 2020
    December 2019
    November 2019
    October 2019
    September 2019
    August 2019
    July 2019
    June 2019
    May 2019
    April 2019
    March 2019
    February 2019
    January 2019
    December 2018
    November 2018
    October 2018
    September 2018
    August 2018
    July 2018
    June 2018
    May 2018
    April 2018
    March 2018
    February 2018
    January 2018
    December 2017
    November 2017
    October 2017
    September 2017
    August 2017
    July 2017
    June 2017
    May 2017
    April 2017
    March 2017
    February 2017
    January 2017
    December 2016
    November 2016
    October 2016
    September 2016
    August 2016
    July 2016
    June 2016
    May 2016
    April 2016
    March 2016
    February 2016
    January 2016
    December 2015
    November 2015
    October 2015
    September 2015
    August 2015
    July 2015
    June 2015
    May 2015
    April 2015
    March 2015
    February 2015
    January 2015
    December 2014
    November 2014
    October 2014
    September 2014
    August 2014
    July 2014
    June 2014
    May 2014
    April 2014
    March 2014
    February 2014
    January 2014
    December 2013
    November 2013

    Categories

    All
    General
    Presentation
    Research
    Review

    RSS Feed

Home

About

Contact Us

Terms & Conditions

Privacy Policy

Copyright Notice

RSS Feed

Proudly powered by Weebly
© The Society of Cancer Management 2017