Navigation Links
Laying bare the not-so-sweet tale of a sugar and its role in the spread of cancer
Date:4/25/2011

BETHESDA, Md., April 25, 2011 Cancer has a mighty big bag of tricks that it uses to evade the body's natural defense mechanisms and proliferate. Among those tricks is one that allows tumor cells to turn the intricate and extensive system of lymphatic vessels into something of a highway to metastasis. Yet research unveiled this week may aid in the development of therapeutics that will put the brakes on such cancer spread, and the researchers who completed the study say the findings may extend to other lymphatic disorders.

In the latest issue of the Journal of Biological Chemistry, the team at the VA San Diego Healthcare System and the University of California, San Diego, reports an important advance in the understanding of the molecular machinery needed for lymphatic cell growth.

"In many carcinomas, lymphatic vessels grow and remodel around and sometimes within tumors. This allows tumor cells to go upstream to the lymph nodes," explains assistant professor Mark Fuster, who led the study. Once tumor cells hitch a ride to the lymph nodes, the disease can be more difficult to fight. "We were trying to understand the mechanisms that turn on the growth of lymphatic vessel cells in the laboratory."

To better understand how tumors get lymphatic vessels to construct an entry ramp for cancerous cells, Fuster's team began by looking at a much-studied lymphatic stimulatory protein that is often over-produced by tumors. The protein migrates from the tumor to a layer of cells within lymphatic vessels known as the endothelium. The tumor-produced protein is officially known as vascular endothelial growth factor C, or VEGF-C for short (pronounced "vej-eff-cee").

"The growth factor VEGF-C lands on a special receiving molecule, or receptor, on the surface of the lymphatic endothelial cells, sending a signal that says it's time for the endothelial cells to replicate and send offshoots," Fuster says. But the team was curious as to whether VEGF-C and its receptor were getting any help from nearby molecules to make that happen. "After all, if there were other players in the mix, that might mean there are other possible drug targets," Fuster explains.

The team focused on a glycan, or sugar, known as heparan sulfate. After some initial clues indicated that destroying the unique sugar on lymphatic endothelial cells would inhibit VEGF-C-dependent growth signaling, Fuster and his team dug in to figure out more about heparan sulfate's role.

"In a cell-based system, we tried to interfere with the components that are involved in making heparan sulfate in lymphatic endothelial cells. We tried inhibiting the production of the sugar and destroying it," Fuster says.

Xin Yin, a postdoctoral research fellow, and Scott Johns, a research associate in the laboratory, both lead authors on the paper, carried out a variety of studies to examine how silencing enzymes in the cell that are responsible for putting the sugar together might alter various cell-growth behaviors and affect VEGF-C's ability to activate its receptor.

"What we found was that giving the glycan-altered cells the VEGF-C resulted in a blunting of the normal growth rate or signaling for growth," Fuster says. "This work shows there may be a key role for heparan sulfate in the initiation of lymphatic vessel-growth responses."

In the setting of cancer, it is thus possible that the presence of heparan sulfate is important for tumor-spurred lymphatic vessel growth: This not only identifies a potential target for anti-cancer drugs, Fuster says, but it may also offer insights about how to stimulate lymphatic vascular growth in diseased parts of the body that, conversely, need lymphatic vessels for normal circulatory and immune functions.

Still, though, Fuster emphasizes that more work remains to be done, because how exactly heparan sulfate interacts with VEGF-C and its receptor remains unclear: "Identifying the importance of heparan sulfate in the growth of living lymphatic systems and identifying its possible importance in mediating the functions of multiple lymphatic growth factors simultaneously remain important considerations for ongoing and future research."


'/>"/>

Contact: Angela Hopp
ahopp@asbmb.org
301-634-7389
American Society for Biochemistry and Molecular Biology
Source:Eurekalert

Related medicine news :

1. Pelosi on Repealing Antitrust Exemption: Health Insurance Companies Will Now Be Playing on the Peoples Field
2. Delaying post-surgical radiation increases risk of breast cancer recurrence in older women
3. More Lower Extremity, Orthopaedic-Related Injuries Occur When Playing on FieldTurf
4. Study: Social influence playing role in surging autism diagnoses
5. Playing a video game before bedtime has only a mild effect on adolescent sleep
6. Lower wages, lack of job opportunities means more Americans delaying adulthood
7. No Benefit Seen in Delaying Infant Vaccinations
8. Playing Games in Prison May Reveal Roots of Psychopathy
9. Playing with pills
10. How football playing robots have the future of artificial intelligence at their feet
11. New health insurance exchanges should be independent, aim for level playing field
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/26/2017)... ... April 26, 2017 , ... Intalere, the healthcare industry leader ... “Make Plans for MACRA,” highlighting the impact of the Medicare Access and ... physicians and other clinicians are reimbursed for the care they deliver in Medicare. ...
(Date:4/26/2017)... ... April 26, 2017 , ... ... thrilled to announce the ATA 2017 President’s Awards recipients, comprised of organizations ... superior healthcare delivery. , The ATA 2017 President’s Awards recognize individuals ...
(Date:4/26/2017)... ... April 26, 2017 , ... Datos Health , developer of a pioneering ... , the largest Electronic Medical Records (EMR) provider in South Africa. By using ... a patient’s remote health progress, empowering the patient to take direct responsibility for their ...
(Date:4/26/2017)... ... April 26, 2017 , ... The National Business ... National Registry of Emergency Medical Technicians and welcomes this organization to ... Dr. Jan G. West, Ph.D. , CEO & Organizational Psychologist at NBRI. “This ...
(Date:4/26/2017)... (PRWEB) , ... April 26, 2017 , ... Miami native ... as a dentist. , “I could have never imagined back in 1991 that this ... said Dr. Gallardo. , Over the last 25 years, Dr. Gallardo has pioneered implant ...
Breaking Medicine News(10 mins):
(Date:4/19/2017)... , April 19, 2017  IRIDEX Corporation (Nasdaq: ... financial results for the first quarter 2017 after the ... Company,s management team will host a corresponding conference call ... Investors interested in listening to the conference ... domestic callers or (703) 326-3030 for international callers, using ...
(Date:4/19/2017)... DALLAS , April 19, 2017 /PRNewswire/ ... that the first patients in Nashville ... in the Lower Esophageal Sphincter Stimulation for GERD (LESS ... device designed to provide long-term reflux control by restoring ... GERD affects nearly 65 million people in ...
(Date:4/19/2017)... April 19, 2017 ... immune response in pets such as canine, avian ... of various types such as Attenuated Live Vaccines, ... DNA Vaccines and Recombinant Vaccines. Attenuated live vaccines ... or bacteria, which have been weakend under laboratory ...
Breaking Medicine Technology: