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Human cancer cells with nuclei (specifically the DNA) stained blue. The central
cells and those on the right are in interphase, so the entire nuclei are labeled.
The cell on the left is going through mitosis and its DNA has condensed.
(TenOfAllTrades/Wikipedia)

Tracking Cancer

Israeli researchers find way
to spot tumor cells in brain.

Shoshanna Solomon

Times of Israel

M

etastatic melanoma is
the deadliest of the skin
cancers; when malignant
melanoma metastasizes to the brain, it is
a death sentence for most patients. The
mechanisms that govern early metastatic
growth and interactions of metastatic
cells with the brain’s microenvironment
are still shrouded in mystery.
Now, a Tel Aviv University study
shows a new way of detecting brain
micrometastases months before they
transform into malignant and inoper-
able growths. According to the research,
micro-tumor cells hijack astrogliosis,
the brain’s natural response to damage
or injury, to support metastatic growth.
This knowledge may lead to the detec-
tion of brain cancer in its first stages and
permit early intervention, the university
said in a statement.
The study was led by Dr. Neta Erez of
the Department of Pathology at TAU’s
Sackler Faculty of Medicine and pub-
lished in Cancer Research.
Erez and her team used mouse models
to study and follow the spontaneous
metastasis of melanoma in the brain.
She and her partners went over all the
stages of metastasis: the initial discovery
of melanoma in the skin, the removal of
the primary tumor, the micrometastatic
dissemination of cancer cells across the
body, the discovery of a tumor and even-
tual death.
Imaging techniques used today can-
not detect micrometastases. Melanoma
patients whose initial melanoma was
removed may believe that everything is
fine for months, or years, following the
initial procedure.
Yet after the removal of the primary
tumor, micrometastatic cells travel across

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the body to the brain or other organs,
and are undetectable at the micro level.
These cells learn to communicate with
cells in their new microenvironment in
the brain — cells which are, at first, hos-
tile to them. Eventually a tumor appears,
and then it generally is too late for treat-
ment.
Erez calls the period of the initial
growth of disseminated micrometastatic
cells in distant organs the “black box” of
metastasis.
“We believe that we have found the
tools to characterize this black box,”
Erez said. “And this is key to developing
therapeutic approaches that may prevent
brain metastatic relapse.”
Every organ in the body has a defense
system — cells — that detects intrud-
ers and is triggered when there is tissue
damage, like from a stroke or a viral
infection. Once activated, these cells
induce an inflammatory response.
“At the earliest stages of metastasis, we
already see astrogliosis and inflamma-
tion. The brain perceives the micrometa-
static invasion as tissue damage, activat-
ing inflammation — its natural defense
mechanism,” Erez said. “We found that
the inflammation unfortunately gets
hijacked by tumor cells that are able
to grow faster and penetrate deeper
because the blood vessels in the brain
are more permeable than in any other
part of the body. We found that all of this
happens very early on.”
Erez is currently studying detailed
molecular pathways in the brain’s bio-
logical response to find a way to block
the metastases.
“We’re hoping to develop the detec-
tion tools for humans that we developed
in mice,” said Erez. “We’re also trying to
find molecular targets that will allow us
to prevent metastasis rather than trying
to treat it.”

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