Brain tumor cells can develop the ability to manufacture
their own molecular road for spreading across the brain.
Researchers of René Bernards' group at the Netherlands Cancer
Institute discovered this mechanism and published their findings in
Cell Reports on July 5th.
Tumor cells in the brain face a difficult challenge when they
want to invade other parts of the brain. Most cells need a
substrate to be able to move, like the extracellular components
collagen and fibronectin. Unlike other organs, the brain lacks
these molecular structures.
Researchers of the Netherlands Cancer Institute investigated how
cells of the most common and aggressive type of primary brain tumor
glioblastoma manage to spread throughout the brain. Patients with
glioblastoma face a very poor prognosis: less than 1 in 10 of them
is still alive after 2 years.
The researchers tested glioblastoma cells and their ability to
migrate through tissue slices of mouse brain. They developed this
3D-model specifically to study the invasive behavior of
glioblastoma cells in a physiological relevant context. Not only
did they discover that the cancer cells that were able to move to
other parts were expressing their own collagens, it also became
clear that cells could develop this ability over time. Further
experiments showed that being able to express collagens was indeed
responsible for the capacity to move.
"This means that glioblastoma cells can have their own asphalt
machine that allows them to move to other parts of the brain", says
group leader Rene Bernards. "They express and excrete
collagens, and use them as their personal road through the brain.
It surprised me that collagens, proteins that are considered to be
a bit boring, are a critical ingredient for invasiveness."
This mechanism of invasion through collagen production may seem
an interesting therapeutic target for glioblastoma treatment, since
an inhibitor of the signal route involved is already available.
This casein kinase 2 (CK2) inhibitor CX4945 indirectly allows
interferon regulatory factor 3 (IRF3) to block collagen production
and thereby reduce the spreading capacity of cancer cells.
Bernards: "The development of this drug was stopped after
unsuccessful early clinical trials in patients with other cancer
types. Testing this compound for applications in glioblastoma might
be useful. However, the problem is that invasion has already
occurred at the time of diagnosis. That's why I doubt that this
approach will become clinically relevant. The main value of our
findings lies in the discovery of how cells can reprogram to become