Paradigm shift: Switch for programmed cell death promotes spread of glioblastoma

March 11, 2008

Malignant tumors have usually lost their ability to destroy themselves by programmed cell death, or apoptosis. Therefore, tumors are often resistant to chemotherapy or radiation therapy, whose effect is based on forcing tumor cells to commit suicide.

This resistance to apoptosis is caused by defects in one of the numerous molecular switches regulating the self-destruction process. This is why scientists have been trying for a long time to restore the formation of these switches in cancer cells and, thereby, to restore their apoptotic ability. Among the key molecular switches is cell surface protein CD95, which is activated by the binding of its partner, CD95L. This triggers a whole cascade of biochemical signals leading to the death of the cell.

At the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Dr. Ana Martin-Villalba and her team have been studying the function of CD95 on glioblastoma cells. Glioblastoma is an extremely aggressive malignant brain tumor that resists all treatments. The cancer grows like a coral and invades surrounding brain tissue with very fine protrusions. Individual, isolated tumor cells can penetrate even further. Thus, surgeons have no chance to completely remove the tumor tissue. In addition, glioblastoma is highly resistant to both chemotherapy and radiotherapy.

Martin-Villalba’s team found large amounts of CD95 on glioblastoma cells, while CD95L was localized primarily at the so-called invasive front – the border between tumor tissue and healthy brain tissue. Despite the presence of both molecules, the cells are resistant to programmed cell death. But this is not all: If CD95 on the surface of glioblastoma cells is activated by CD95L, this leads to the production of a protein called MMP9, which is known to be a molecular scissors. MMP9 cuts through the network of interwoven protein fibers that separate different tissue layers of the body from each other. With the aid of these protein scissors, tumor cells invade healthy tissue and form the dangerous protrusions that penetrate deep into the brain tissue.

The result showed the scientists a way how to stop the invasion of glioblastoma: They treated mice that had been transplanted glioblastoma with an antibody that blocks CD95. As a result, the migration of cancer cells ceded.

“This is almost a paradigm shift,” says Ana Martin-Villalba. “Up to now, the goal has been to promote formation of CD95 and CD95L in tumor cells. In the case of glioblastoma, we now have to warn against this approach: This would only additionally support the spread of the tumor. The goal is rather to block activation of CD95.” However, it is currently not possible to investigate this treatment approach in humans, because a useable antibody against human CD95 protein is not yet available.

Source: Helmholtz Association of German Research Centres

Explore further: Surprising new way to kill cancer cells

Related Stories

Surprising new way to kill cancer cells

March 21, 2014
Northwestern Medicine scientists have demonstrated that cancer cells – and not normal cells – can be killed by eliminating either the FAS receptor, also known as CD95, or its binding component, CD95 ligand.

Trial combining anti-cancer drug and radiotherapy may lead to treatment for brain tumor

September 30, 2013
Results from a clinical trial of a new treatment for glioblastoma suggest that researchers may have found a new approach to treating this most aggressive of brain tumours, as well as a potential new biological marker than ...

Recommended for you

African Americans face highest risk for multiple myeloma yet underrepresented in research

November 23, 2017
Though African-American men are three times more likely to be diagnosed with multiple myeloma, a type of blood cancer, most scientific research on the disease has been based on people of European descent, according to a study ...

Encouraging oxygen's assault on iron may offer new way to kill lung cancer cells

November 22, 2017
Blocking the action of a key protein frees oxygen to damage iron-dependent proteins in lung and breast cancer cells, slowing their growth and making them easier to kill. This is the implication of a study led by researchers ...

One-size treatment for blood cancer probably doesn't fit all, researchers say

November 22, 2017
Though African-American men are three times more likely to be diagnosed with a blood cancer called multiple myeloma, most scientific research on the disease has been based on people of European descent, according to a study ...

One in four U.S. seniors with cancer has had it before

November 22, 2017
(HealthDay)—For a quarter of American seniors, a cancer diagnosis signals the return of an old foe, new research shows.

Combination immunotherapy targets cancer resistance

November 22, 2017
Cancer immunotherapy drugs have had notable but limited success because in many cases, tumors develop resistance to treatment. But researchers at Yale and Stanford have identified an experimental antibody that overcomes this ...

Researchers discover specific tumor environment that triggers cells to metastasize

November 21, 2017
A team of bioengineers and bioinformaticians at the University of California San Diego have discovered how the environment surrounding a tumor can trigger metastatic behavior in cancer cells. Specifically, when tumor cells ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.