Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Laying bare the not-so-sweet tale of a sugar and its role in the spread of cancer

26.04.2011
Scientists close in on molecular moves that let tumor cells act as stowaways in lymphatic system

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."

Fuster is affiliated with the VA San Diego Healthcare System and the University of California, San Digeo. His team's article was named a "Paper of the Week" by the Journal of Biological Chemistry's editorial board, landing it in the top 1 percent of all papers published over the year in the journal. The online version of the article can be found at http://www.jbc.org/content/286/17/14952, and it will appear in the April 29 print issue of the journal.

The team's project was funded by a career development award to Fuster from the U.S. Department of Veterans Affairs, by the American Cancer Society, by the Uniting Against Lung Cancer Foundation, and by Program Project funding by the National Institutes of Health.

Other team members included Roger Lawrence, Ding Xu, Krisanavane Reddi, Joseph Bishop and Judith Varner.

About the American Society for Biochemistry and Molecular Biology

The ASBMB is a nonprofit scientific and educational organization with more than 12,000 members worldwide. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, at nonprofit research institutions and in industry. The Society's student members attend undergraduate or graduate institutions.

Angela Hopp | EurekAlert!
Further information:
http://www.asbmb.org

More articles from Life Sciences:

nachricht Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>