Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cancer researchers describe gene that halts spread of aggressive childhood cancer

05.01.2006


A team of cancer researchers has shown that a gene commonly lost during neuroblastoma tumor formation, one of the most aggressive cancers in babies and children, is in fact a "metastasis suppressor" gene. The researchers, from the Moores Cancer Center at the University of California, San Diego (UCSD) Medical Center and St. Jude Children’s Research Hospital in Memphis, also describe how the gene, caspase 8, works.



The findings, published in the January 5 issue of the journal Nature, provide important new insights into the biology of metastatic disease and lay the necessary groundwork for developing targeted therapies designed to halt the spread of neuroblastoma, and possibly other cancers.

"A major problem with cancer is not necessarily the primary tumor formation, but the ability of some tumor cells within that primary tumor to metastasize, or travel to distant sites, where they develop new tumors," said David Cheresh, Ph.D., senior author on the paper and Associate Director for Translational Research at the Moores UCSD Cancer Center. Cheresh is also a professor of pathology at the UCSD School of Medicine.


Caspase 8’s normal role is to act as a suicide gene, killing the cell it is housed within in response to cues from the immune system. The UCSD group had previously shown, in normal human cells, that caspase 8 can be activated even without signals from the immune system, particularly when the cell is present in a foreign location. This acts as a mechanism to ensure the cells would survive only in appropriate tissues; for example, liver cells in liver tissue and skin cells in skin tissue.

"The exciting point of the new research is that we are finding that even tumor cells will try to make sense of their location, and when they cannot, they will often activate this suicide pathway," said Dwayne Stupack, Ph.D., first author on the paper and assistant professor of pathology at UCSD.

The team showed that when a neuroblastoma cell attempts to migrate away from the primary tumor and encounters new tissues, cell-surface molecules called integrins detect that the cell is in "foreign territory" and send "death" signals into the cell. These signals activate caspase 8, which then instructs the cell to commit suicide. The researchers have coined this mechanism "integrin-mediated death."

Some cancer cells, however, have found a way to escape the normal death-promoting machinery the body has developed. These cells may suppress or even delete caspase 8, freeing themselves to become much more aggressive and survive in distant sites in the body.

"We’ve shown now in animals and human tissue that as soon as the neuroblastoma cells lose caspase 8, suddenly you have a much more aggressive disease," said Stupack. "This explains why we see the loss of caspase 8 in 70 percent of aggressive neuroblastomas in children."

Neuroblastoma is a solid tumor cancer that usually originates in the abdomen near the kidneys. In the majority of cases (about 70 percent), by the time of diagnosis the disease has already metastasized. The average age at diagnosis is two years old.

"It is clear this gene is a deciding factor in whether or not a cancer cell becomes metastatic, yet, surprisingly, it does not appear to be involved at all in the initial formation of the cancer," said Stupack. "As such, it is one of only a handful of true metastasis suppressor genes currently known."

A number of other cancers may use this same mechanism for regulating their metastatic properties, which the researchers are now studying. Caspase 8 loss or suppression is seen in about 70 percent of small cell lung cancer, about 10 percent of colon cancer and about 35 percent of medulloblastoma. While genetic mutation will sometimes delete both copies of the caspase 8 gene, typically the gene is simply silenced.

This paper opens up a new way of thinking about cancer therapy.

"Now we have a roadmap for attacking not just the primary cancer but the metastatic cascade, the metastatic disease process, as well," said Cheresh. "That is new, and very exciting. We now know the Achilles heel of the metastatic tumor cell. If we can develop drugs targeted at restoring caspase 8, we may be able to stop metastasis. That now appears feasible."

The study was co-authored by a team from St. Jude that included Tal Teitz, Ph.D., Peter Houghton, M.D., and Jill Lahti, Ph.D., as well as by UCSD scientists Matthew Potter, Ph.D., and David Mikolon. Lahti, the senior scientist in the St. Jude group, has collaborated with Stupack for several years.

Nancy Stringer | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-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: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>