Wednesday, November 18, 2009
Just as fly paper captures insects, an innovative new device with
nano-sized features developed by researchers at
UCLA is
able to grab cancer cells in the blood that have broken off from a
tumor.
These cells, known as circulating tumor cells, or CTCs, can
provide critical information for examining and diagnosing cancer
metastasis, determining patient prognosis, and monitoring the
effectiveness of therapies.
Metastasis - the most common cause of cancer-related death in
patients with solid tumors - is caused by marauding tumor cells
that leave the primary tumor site and ride in the bloodstream to
set up colonies in other parts of the body.
The current gold standard for examining the disease status of
tumors is an analysis of metastatic solid biopsy samples, but in
the early stages of metastasis, it is often difficult to identify a
biopsy site. By capturing CTCs, doctors can essentially perform a
"liquid" biopsy, allowing for early detection and diagnosis, as
well as improved treatment monitoring.
To date, several methods have been developed to track these
cells, but the UCLA team's novel "fly paper" approach may be faster
and cheaper than others - and it appears to capture far more
CTCs.
In a study published this month in the journal Angewandte
Chemie, the UCLA team developed a 1-by-2-centimeter silicon chip
that is covered with densely packed nanopillars and looks like a
shag carpet. To test cell-capture performance, researchers
incubated the nanopillar chip in a culture medium with breast
cancer cells. As a control, they performed a parallel experiment
with a cell-capture method that uses a chip with a flat surface.
Both structures were coated with anti-EpCAM, an antibody protein
that can help recognize and capture tumor cells. The researchers
found that the cell-capture yields for the UCLA nanopillar chip
were significantly higher; the device captured 45 to 65 percent of
the cancer cells in the medium, compared with only 4 to 14 percent
for the flat device.
"The nanopillar chip captured more than 10 times the amount of
cells captured by the currently used flat structure," said lead
study author Dr. Shutao Wang, a postdoctoral researcher at both the
Crump Institute for Molecular Imaging at the David Geffen School of
Medicine at UCLA and the California NanoSystems Institute at
UCLA.
Wang noted that the nano-size scale and the unique surface
topography of the UCLA nanopillar chip may help it interact with
nano-size components on cellular surfaces in the blood, enhancing
capture efficiency.
The time required for CTC detection using CellSearch, a
technology currently approved by the U.S. Food and Drug
Administration, is upwards of three to four hours, according to
study author Dr. Hao Wang, a postdoctoral researcher at the Crump
Institute and the California NanoSystems Institute at UCLA. The
UCLA study found an optimal detection time of only two hours using
nanopillar chips.
The nanopillar chip uses a common chamber slide, which fits into
standard laboratory cell incubators. After the chip has been
incubated and immunofluorescence-stained, an automated fluorescence
microscope is used to identify and count the CTCs. The very simple
device setting on the chamber slide allows multiple CTC detections
to occur at the same time.
"We hope that this platform can provide a convenient and
cost-efficient alternative to CTC sorting by using mostly standard
lab equipment," said senior study author Dr. Hsian-Rong Tseng,
associate professor of molecular and medical pharmacology at the
Crump Institute and the California NanoSystems Institute.
The next step is more clinical research and possible studies
with "break-away" cancer cells in patients' blood, as well as in
other body fluids, such as urine and abdominal fluids, according to
Tseng, who is also a researcher at UCLA's Jonsson Comprehensive
Cancer Center.
The study was funded by the National Cancer Institute's Centers
of Cancer Nanotechnology Excellence and the NanoSystems Biology
Cancer Center.
SOURCE