Johns Hopkins engineers have invented a method that
could be used to help figure out how
cancer cells break free from neighboring tissue, an
"escape" that can spread the disease to other
parts of the body. The new lab-on-a-chip, described in the
March issue of the journal Nature
Methods, could lead to better cancer therapies.
Peter Searson
|
"Studying cell detachment at the subcellular level is
critical to understanding the way cancer
cells metastasize," said principal investigator Peter
Searson, Reynolds Professor of Materials Science
and Engineering in the Whiting School of Engineering.
"Development of scientific methods to study
cell detachment may guide us to prevent, limit or slow down
the deadly spreading of cancer cells."
Searson's team's research focuses on a missing puzzle
piece in the common but unfortunate
events that can occur in cancer patients.
For example, cancer that starts in the breast
sometimes spreads to the lungs. That's because
tumor cells detach and travel through the bloodstream to
settle in other tissues. Scientists have
learned much about how cancer cells attach to these
surfaces, but they know little about how these
insidious cells detach because no one had created a simple
way to study the process.
Searson and two other scientists from the Whiting
School have solved this problem with a lab-
on-a-chip device that can help researchers study cell
detachment. With this device, they hope to
discover exactly how cancer cells spread.
Denis Wirtz
|
The lab-on-a-chip device consists of an array of gold
lines on a glass slide. Molecules promoting
the formation of cell attachments are tethered to the gold
lines like balloons tied to string. A cell is
placed on the chip, atop these molecules. The cell spreads
across several of the gold lines, forming
attachments to the surface of the chip with help from the
molecules. Then, the tethered molecules
are released from one of the lines by a chemical reaction,
specifically by "electrochemical reduction,"
Searson said. Where these molecules are detached, that
portion of the cell loses its grip on the
surface of the chip. This segment of the cell pauses for a
moment and then contracts forcefully
toward its other end, which is still attached to the chip.
The researchers were able to film this "tail
snap" under a microscope.
"It's very dramatic," said Denis Wirtz, a professor of
chemical
and biomolecular engineering. "The cell stretches way,
way out across the chip, and then, on command, the tail
snaps toward the
body of the cell."
Cells survive this programmed-release process and can
be tested again and again, the
researchers said.
Bridget Wildt, a materials science and engineering
doctoral student in Searson's lab, used the
device to perform and record movies of the live-cell
experiments. Wildt tested cells from the
connective tissue of mice during these experiments, but the
team plans to try other types of cells in
the future.
Bridget Wildt
|
"In the movies, you can see that the cell doesn't move
immediately after the chemical reaction
is triggered. We refer to this phenomenon as the induction
time of the cell," Wildt said. "After this
induction time, the cell then snaps back and contracts. We
analyze the rate of the cell's contraction
and then compare this information to separate cells
released under different conditions using
chemicals called inhibitors. From these results we are
beginning to understand the processes that
regulate cell detachment at the molecular level," she
said.
The researchers have speculated that the induction
time for cancer cells, as compared to
noncancerous cells, would be shorter because cancer cells
are more pliable. In the near future, Wildt
said, they plan to test this hypothesis in experiments with
cancer cells. If this assumption proves
correct, it may give them a tool to differentiate between
cancerous and noncancerous cells.
Searson is director and Wirtz is associate director of
the Johns Hopkins Institute for
NanoBioTechnology. Their work was supported by grants from
the National Institutes of Health,
National Science Foundation and Howard Hughes Medical
Institute. Wildt's participation in the
research was funded by the Achievement Rewards for College
Scientists Foundation.
The study, written by Wildt, Wirtz and Searson, can be
viewed online at:
www.nature.com/nmeth/journal/v6/n3/full/
nmeth.1299.html.
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