Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Migration Negation

07.11.2014

Blocking a receptor may combat cancer metastasis

Most cancer deaths occur because of metastasis, yet progress in preventing and treating migratory cancer cells has been slow.


Like a transformer surge that makes birds on a wire take flight, new research has found that the receptor Frizzled-2 can induce cancer cells to migrate. Image: O'Reilly Science Art

“It’s been particularly challenging to design drugs that work against metastasis,” said Taran Gujral, research fellow in systems biology at Harvard Medical School. “Unfortunately, many cancers aren’t detected until after they’ve already metastasized.”

Gujral and colleagues have now identified a cellular culprit that should help researchers better understand how metastasis begins. Their findings may also inform the design of new treatments to combat it.

As reported Nov. 6 in Cell, the team discovered that an overabundance of a cell receptor called Frizzled-2, along with its activator, Wnt5, appears to raise a tumor’s likelihood of metastasizing by triggering a process known as the epithelial-mesenchymal transition, or EMT.

Get more HMS news here

EMT normally plays a role in human development, allowing certain cells to become mobile and invasive so they can move around and form new structures in the growing embryo. Previous studies have linked EMT to cancer metastasis, where tumor cells acquire those properties to disastrous effect. The question has been: How exactly does that happen?

“This study makes big headway on an extremely important medical problem: what makes one type of tumor metastasize and another type not,” said Marc Kirschner, John Franklin Enders University Professor of Systems Biology at HMS, chair of the Department of Systems Biology and co-senior author of the paper.

“On a basic biology level, it also reports the unexpected discovery of a brand-new cell signaling pathway,” Kirschner added.

After learning the importance of Frizzled-2, the researchers developed an antibody to block it. The antibody curbed metastasis in mice with certain types of tumors.

The researchers are now pursuing further studies of the antibody with the hope that it can one day be turned into a metastasis-fighting drug.

“Discovering that Frizzled-2 and Wnt5 play a causal role in EMT and metastasis is directly actionable,” said co-senior author Gavin MacBeath, lecturer in systems biology at HMS and senior vice president at Merrimack Pharmaceuticals.

“Frizzled-2 provides a promising new therapeutic target to prevent or delay metastasis, and both Frizzled-2 and Wnt5 are potential biomarkers that can be used to identify which patients are most at risk of metastasis and could benefit from Frizzled-2-directed therapy,” MacBeath said.

The study also illuminates an important biological process and may contribute to better predictions of metastasis likelihood and patient survival.

Researchers had known that cell signaling pathways activated by the Wnt (“wint”) protein family influence EMT, but they weren’t sure how. First author Gujral and his colleagues examined various Wnt signals, and the Frizzled family of receptors they bind to, in many cancer cell lines.

They found that Wnt5 and its receptor, Frizzled-2, were present at higher than normal levels in metastatic liver, breast, lung and colon cancer cell lines. In tissue samples from 48 cancer patients, Frizzled-2 was higher in late-stage cancers than in early-stage cancers. And patients with late-stage liver cancer who had high levels of Frizzled-2 had lower survival rates.

The team then painstakingly pieced together the players linking Wnt5 with the onset of metastatic behavior and discovered a previously unknown Wnt pathway. Frizzled-2, it turned out, could activate STAT3, which is known to drive cancer through EMT.

In addition to exploring Frizzled-2 as a new drug target, a potential biomarker for metastasis and a possible addition to the factors that predict patient survival, next steps include nailing down other pathway players to gain a full understanding of EMT in cancer and beyond.

“Although it will take time to determine whether this discovery can be translated into a novel therapeutic option for patients, I am very excited about the potential,” said MacBeath. “Significant advances in combating cancer must come from new approaches, and developing precision therapeutics that prevent metastasis provides a promising and different way to fight this devastating disease.”

Other authors on the paper were Peter Sorger, Otto Krayer Professor of Systems Pharmacology at HMS; Leonid Peshkin, lecturer on systems biology at HMS; and Marina Chan, former postdoctoral fellow in systems biology in the MacBeath Lab.

This work was funded by the National Institutes of Health (grants R01 GM072872, P50 GM68762, U54 HG006097, R01 HD073104 and R01 GM103785).

David Cameron | EurekAlert!
Further information:
http://hms.harvard.edu/news/migration-negation

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>