Remy Elbez, a doctoral student in applied physics, takes a sample of a solution that contains magnetized cervical cancer cells. He will place several drops of the solution in a special magnetic field. Then, after placing the whole apparatus under a microscope, he can watch the cells spin on a screen and determine their shape and status from their rotation rates. This new technique could help doctors understand the process of cancer metastasis. Photo: Nicole Casal Moore |
A
technique that lets researchers monitor single cancer cells in real
time as they float in liquid could help doctors study the breakaway
tumor cells that cause metastasis. Metastasis is the process of the
disease spreading through the body.
The
approach, developed at the University of Michigan, could also pave the
way for new types of targeted therapies that go beyond personalized
medicine, researchers say.
“We’re
looking toward individualized treatment, not just to the person, but to
the cell,” said Remy Elbez, a doctoral student in applied physics. He
is a co-author of a paper on the work published Dec. 13 in PLoS ONE.
In
recent years, researchers have come to understand that not all cells in
a cancerous tumor share the same genetic code. This means some are more
difficult to kill than others. And techniques that enable single-cell
study are in demand. Approaches that process many cells at once aren’t
as useful for researchers who want to look, for example, at a small
number of cells that a particular cancer drug left alive.
One
particularly dangerous type of cancer cell that scientists want to know
more about is the circulating tumor cell. These cells have separated
from the original tumor and set off in the bloodstream to invade distant
tissues. Scientists know that they’re different from the cells that
stay put. They don’t divide rapidly, for example. At the same time,
they’re difficult to study for several reasons. They’re hard to find
because they only make up less than one in a trillion blood cells. And
they operate in motion, so tamping them down to a Petri dish doesn’t
reveal their true nature.
“In
our suspension, the cells can flow freely and behave closer to the way
they do in the body,” said Raoul Kopelman, the Richard Smalley
Distinguished University Professor of Chemistry, Physics and Applied
Physics, and a professor in biomedical engineering and biophysics.
“This is a completely new technique for monitoring a single cell’s growth and death processes in real time in a suspension.”
A
better understanding of circulating tumor cells could one day lead to
therapies that focus on them, and help to block cancer from spreading
beyond its initial site, the researchers say. That could lengthen
patients’ lives.
“It
is the consequences of metastasis that lead to the death of most cancer
patients,” said Kenneth Pienta, M.D., a professor of internal medicine
and urology who studies cancer metastasis.
Their
approach uses magnets to rotate cancer cells in a way that lets their
spinning speed reveal their shape and status. A growing, dividing or
dying cell spins slower in the researchers’ system. To demonstrate that
their technique works, they embedded cervical cancer cells with
commercially available magnetic nanoparticles in a solution. They then
placed the solution in a magnetic field that rotates fast enough to
achieve an asynchronous rotation rate. Because of the asynchronous
rotation, the cells are more affected by drag and the larger, dying or
dividing cells rotate much slower, and with specific patterns.
“For
the first time, we enable the cell itself to be the sensor. It can tell
us when it is dying,” Elbez said. “Other methods such as fluorescent
dyes rely on indirect evidence.”
The
new system could advance drug testing, the researchers say. It could
enable scientists to zero in on the most resistant cells.
It
could also pave the way for more personalized cancer treatment. In
essence, mini drug-trials could be conducted on a small sample of tumor
cells before subjecting patients to rounds of chemotherapy that may or
may not work.
“Personalized
cancer treatments allow for treatment of the right patient at the right
time with the right medicine,” Pienta said. “More importantly, it can
avoid treatment with the wrong medicine, which does the patient no good
and wastes money.”
The
paper is titled “Nanoparticle induced cell magneto-rotation: Monitoring
morphology, stress and drug sensitivity of a suspended single cancer
cell.” In addition to Elbez, Kopelman and Pienta, other co-authors are
Brandon McNaughton and Lalit Patel. The researchers are working to
commercialize this technology. McNaughton is a founder of the U-M
start-up Life Magnetics. The research is funded by the National
Institutes of Health.
