The process of metastasis, by which cancer cells travel from a tumor site and
proliferate at other sites in the body, is a serious threat to cancer patients.
According to the US National Cancer Institute, most recurrences of cancer are
metastases rather than “new” cancers. Virtually all types of cancer can spread
to other parts of the body, including the brain.
Once metastatic melanoma
cells are entrenched in the brain, patients typically have only a short time to
Now Prof. Isaac Witz and his team at Tel Aviv University’s
department of cell research and immunology are delving deeper into what attracts
metastatic melanoma cells to the brain and how they survive and prosper in this
Their experiments have revealed that melanoma cells produce
receptors for two chemokines – a family of small proteins secreted by cells –
that are present in the brain tissue.
These receptors may act as a homing
device, drawing the cancerous cells to the brain. Their research was published
in the International Journal of Cancer.
“These interactions between the
chemokines in the brain and the melanoma cell receptors could be potential
targets for new therapies,” Witz says. “With medications that suppress these
molecules, you could hope to interfere with this specific
Although metastasis is a well-understood process, researchers
are still trying to uncover the underlying mechanisms of why cancer cells begin
to migrate in the first place. It is also crucial to understand what allows them
to sustain themselves, divide and propagate once they have arrived at their new
To better understand metastasized melanoma cells in the brain,
the researchers cultured brain tissue in the lab, then analyzed all of the
materials expressed by the cells. They identified certain chemokine receptors in
brain-metastasizing melanoma cells and corresponding chemokines in the brain
tissue, which could ultimately be responsible for the cancer cells’ being
“attracted” to the brain. If a certain chemokine is released from the brain, and
the melanoma cells have the appropriate receptors, a chemical attraction will
take place where the melanoma cells would be drawn to wherever the chemokine
The researchers have also developed a method to compare metastatic
and non-metastatic cells with identical genetic backgrounds. Though they are
derived from the same cancer, some of these cells become metastatic, while
others do not.
“This is a good way for us to concentrate on the genes
that are specific to metastatic cells. Because we have these two types of
cellular variants, where only one goes to the brain and metastasizes, it’s an
important tool” for future research, Witz explains.
The researchers have
found that mice that are inoculated with non-metastatic cells do end up with
melanoma cells in the brain, but they are dormant and do not generate overt
metastasis. The key is to discover why these originally identical cells differ –
why the non-metastatic cells don’t develop in the same way. Understanding the
process will help scientists to “duplicate what nature does and prevent these
cells from becoming metastatic,” concludes Witz. “If there already is
metastasis, it is too late – so what we want to do is to prevent development by
understanding the mechanism that keeps the non-metastatic cells dormant.”