2009-ASCB-Press-Book - page 5

T h e A m e r i c a n s o c i e t y f o r C e l l B i o l o g y
News from
The American Society
for Cell Biology
49th Annual Meeting
San Diego, CA
December 5–9, 2009
Imaging metastasis
10:00 am, U.S. Pacific Time
Sunday, December 6, 2009
Erik Sahai
Cancer Research UK
London Research Institute
44 Lincoln’s Inn Fields
London WC2A 3PX, UK
+44 (0)20 72693165
Author presents
Sunday, December 6, 2009
8:35–8:55 am
Minisymposium 1: Cancer Cells
Program 2
Ballroom 20A
Imaging the Metastatic Process
E. Sahai, S. Giampieri,
S.E. Pinner
Tumor Cell Biology Laboratory,
Cancer Research UK, London
Research Institute, London, UK
New imaging follows individual
breast cancer cells as they go
metastatic, revealing a deadly
transition controlled by switching
messenger genes on and then
off again
reast cancer cells escaping from a
primary tumor either go it alone
or in groups. In cancer, that choice
may make all the difference. Alone is
more deadly because single tumor cells
can spread through the blood and me-
tastasize at remote sites around the body.
Cancer cells in groups are limited to trav-
el through the lymphatic system, which
keeps them local. The difference, accord-
ing to Erik Sahai and colleagues at Cancer
Research UK’s London Research Institute,
stems from a series of messenger genes
under the control of transforming growth
factor beta (TGFß), which regulates cell
growth and movement.
The researchers used an advanced
microscopy and analysis technique to
image the movement of cancer cells
leaving a primary tumor site in mice. The
cancer cells were tagged with a “reporter”
protein that glowed blue when the TGFß
cell messenger system was active. The
findings showed that TGFß controlled a
set of genes that need to be first turned
on and then off to enable breast cancer
cells to spread through the blood.
Intravital imaging shows a mammary tumor (700x400 microns). Cancer cells are shown
with a green membrane label. Tumor-associated macrophages are in red. The surrounding
extracellular matrix is shown in purple.
The researchers found that in the
presence of a signal fromTGFß, single
cells broke away from the main tumor
and spread via the blood to other tissues
and organs, including the lungs. But the
absence of a TGFß signal prevented single
cells from breaking away. Instead the
tumor spread via clumps of cells in the
lymphatic system, which can spread lo-
cally but not through the blood or lungs.
Sahai believes that these messenger
genes are a promising target for drugs to
block the metastatic breast cancer route.
“The results helped us to find the set of
genes that are behind the spread of breast
cancer—and that the genes need to be
first turned on and then off in order for
single cancer cells to be able to ‘relocate.’”
Sahai says that his imaging method
allows his team to analyze cell signaling
“live” while watching individual cancer
cells make the crucial transition to me-
tastasis. It gives science a closer look at
a process that has been largely hidden.
“Surprisingly little is known about the way
cancer cells spread through the body be-
cause it is so incredibly difficult to study,”
says Sahai. “In a medium-sized tumor
there could be a billion cells—and only a
small proportion might break away and
spread. So it is like trying to find—and to
understand—a moving needle in a very
big haystack.”
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