Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Newly discovered behavior in cancer cells signals dangerous metastasis

19.09.2006
The most aggressively malignant cancer cells have a "toggle switch" that enables them to morph into highly mobile cells that invade other tissues and then nest comfortably in their new surroundings, a new study in rats suggests.

This picture of how cancer cells shift between two alternating states -- travelers and nesters -- represents a new understanding of how cancer metastasizes, or spreads to other parts of the body, said the Duke Comprehensive Cancer Center researchers who conducted the study.

"Understanding this toggle switch might ultimately enable scientists to find ways to stop cells from metastasizing, which is the most deadly trait of cancer," said the study's lead investigator, Mariano Garcia-Blanco, M.D., Ph.D., professor of molecular genetics and microbiology.

The researchers will publish their findings in the Sept. 19, 2006, issue of the journal Proceedings of the National Academy of Sciences, now available on line. The research was funded by the National Cancer Institute.

Until now, scientists have believed that cancer cells must transform permanently from stationary epithelial cells into migratory mesenchymal cells in order to metastasize.

The Duke team discovered that highly malignant cells are equal parts epithelial and mesenchymal, transitioning between the two as their surroundings necessitate. The proteins that the cell produces dictate which way the cell shifts.

In a classic example of survival of the fittest, a cancer cell's ability to toggle between epithelial and mesenchymal enables the most malignant cells to aggressively invade and then peacefully adapt in unfamiliar territory, the scientists said.

"The prevailing notion has been that the more mesenchymal the cancer cells, the more mobile and metastatic they would be," Garcia-Blanco said. "In reality, aggressive cancer cells are not homogenous, but are extremely versatile in their ability to adapt as their survival needs shift."

The researchers discovered this transition in cancer cells when they observed an error in "alternative splicing," a key element of the genetic copying program inside cells. Alternative splicing determines how the DNA is chopped into pieces and then reassembled. The order in which DNA is reassembled determines which proteins the gene produces.

In cancer cells, the splicing machinery goes awry -- as do myriad functions within the cells. When the splicing process proceeds one way, the cells become mesenchymal. Spliced another way, the cells turn epithelial.

To determine which way a cancer cell would turn, the scientists constructed a fluorescent "reporter" -- a protein that illuminates if the cell turns epithelial but lies dormant if the cell reverts to mesenchymal state.

By following the reporter's illumination within cancer cells in rats, the team viewed the very process of alternative splicing as it occurred in the tumors. The researchers were able to visualize specific portions of DNA, called exons, to see if they were included or excluded in the splicing process as the cell transformed.

"We found that the regulation of alternative splicing is different in mesenchymal versus epithelial cells," Garcia-Blanco said. "A particular exon, FGFR2 IIIc, is silenced in mesenchymal cells but is active in epithelial cells.

"We can visualize the genes as they are dynamically changing," he said. "We can define the cell types by observing their splicing patterns."

According to Garcia-Blanco, the cellular switch that is believed to guide the regulation of splicing is a protein called Fox. Both mesenchymal and epithelial cells produce Fox, but the protein is active only in epithelial cells, Garcia-Blanco said.

Fox also may have an accomplice or "co-factor" in or around epithelial cells that prompts it to activate, the researchers said. They speculate that this co-factor could be activated by contact with stroma --the supporting structural cells of a tumor -- because the stroma is where the majority of epithelial-type cancer cells were observed. Their heavy presence implies that the stroma may have induced the cancer cells to revert to epithelial when they reached a new destination, so they could stabilize to populate a new tumor site.

"Our findings validate that tumors are highly complex in their behavior and don't necessarily need a gene mutation to alter their behavior," said Sebastian Oltean, M.D., Ph.D., research associate and first author of the journal article.

"Alterations in gene splicing can be much more subtle in nature but still have a major impact on the cancer cell and can be targets of therapy."

The team's next step is to determine precisely what controls the toggle mechanism in cancer cells, Garcia-Blanco said. Identifying the various steps that occur during the natural progression of tumors could lead to therapies for blocking metastasis, he said.

Rebecca Levine | EurekAlert!
Further information:
http://www.mc.duke.edu

Further reports about: Garcia-Blanco discovered epithelial mesenchymal splicing

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>