February 25, 2009
New findings measure precise impact of fat on cancer spread
WEST LAFAYETTE, Ind. -
Researchers at Purdue University have precisely measured the impact of
a high-fat diet on the spread of cancer, finding that excessive dietary
fat caused a 300 percent increase in metastasizing tumor cells in
laboratory animals.
The researchers used an imaging technique to
document how increasing fat content causes cancer cells to undergo
changes essential to metastasis. Then they used another technique to
count the number of cancer cells in the bloodstream of mice fed a
high-fat diet compared to animals fed a lean diet.
The
findings suggest that the combined tools represent a possible new
diagnostic technique to determine whether a patient's cancer is
spreading, said Ji-Xin Cheng, an assistant professor in Purdue's Weldon
School of Biomedical Engineering and Department of Chemistry.
"It is generally accepted that diet and obesity
are accountable for 30 percent of preventable causes of cancer, but
nobody really knows why," Cheng said. "These findings demonstrate that
an increase in lipids leads directly to a rise in cancer metastasis."
Researchers have theorized that tumor cells need
more lipids than ordinary tissues to provide energy and material for
tumor growth and metastasis.
"Before this work, however, most of the evidence
was anecdotal, but here we present a mechanistic study," said Thuc T.
Le, a National Institutes of Health postdoctoral fellow at Purdue who
is working with Cheng.
Findings were detailed in a paper published on
Jan. 30 in the journal BMC Cancer. The paper was written by Le; Terry
B. Huff, a graduate research assistant in Purdue's Department of
Chemistry; and Cheng. The research is supported by the Purdue Cancer
Center.
The researchers implanted a cancerous lung tumor
under the skin in each of the mice studied, and the animals were
separated into two groups: one fed a high-fat diet and the other a lean
diet.
The researchers then used an imaging method
called coherent anti-Stokes Raman scattering, or CARS, to document how
increasing lipids from fat intake induces changes to cancer cell
membranes. Those changes, including processes called membrane phase
separation and membrane rounding, enhance cancer metastasis.
"If the cancer cells don't have excess lipids
they stick together and form very tight junctions in tumors, but
increasing lipids causes them to take on a rounded shape and separate
from each other," Le said.
The change in shape is critical to the ability of cancer cells to separate and spread throughout the body via the bloodstream.
The researchers then used another technique,
called intravital flow cytometry, to count the number of cancer cells
in the bloodstream of the mice. The technique works by shining a laser
though the skin and into blood vessels, where the dyed cancer cells are
visible.
Results showed the increase in lipids had no
impact on the original tumors implanted in the mice. However, the rate
of metastasis rose a dramatic 300 percent in the mice fed a high-fat
diet.
The researchers later also examined the animals'
lungs and counted the number of cancer cells that had migrated to the
lungs as a result of metastasis. Those findings supported the other
results showing increased metastasis in animals fed a high-fat diet.
The researches used the imaging and
cell-counting tools to document that linoleic acid, which is
predominant in polyunsaturated fats, caused increasing membrane phase
separation, whereas oleic acid, found in monounsaturated fats, did not.
Increased membrane phase separation could improve the opportunity of
circulating tumor cells to adhere to blood vessel walls and escape to
organs far from the original tumor site. The new findings support
earlier evidence from other research that consuming high amounts of
polyunsaturated fat may increase the risk of cancer spreading.
The findings suggest that combining CARS and
intravital flow cytometry represents a possible new diagnostic tool to
screen patients for cancer. The tool can be used to count lipid-rich
tumor cells circulating in a patient's blood by shining a laser through
the skin and into blood vessels. Because lipids can be detected without
the need for dyes, the technique might be developed into a convenient
method to diagnose whether a patient's cancer is spreading
aggressively, Cheng said.
"These findings open the possibility of an
entirely new, relatively simple method for diagnosing whether cancer is
metastasizing," he said.
Future work will focus on not only how obesity
increases metastasis but also how it might play a direct role in
initiating the development of cancers.
The research has been funded by the National Institutes of Health.
Writer: Emil Venere, (765) 494-4709, [email protected]
Sources: Ji-Xin Cheng, (765) 494-4335, [email protected]
Thuc T. Le, (765) 496-9717, [email protected]
Purdue News Service: (765) 494-2096; [email protected]
Note to Journalists:
Ji-Xin Cheng pronounces his name Jee-Shin Cheng. Thuc Le pronounces his
name Tuck Lay. An electronic copy of the research paper is available
from Emil Venere, (765) 494-4709, [email protected]
IMAGE CAPTION:
Researchers
at Purdue have precisely measured the impact of a high-fat diet on the
spread of cancer, finding that excessive dietary fat caused a 300
percent increase in metastasizing tumor cells in laboratory animals.
Here, lipid-rich cancer cells (the two round objects) attach to
collagen fibrils, simultaneously visualized using coherent anti-Stokes
Raman scattering and sum frequency generation imaging. Cancer cells
attach to collagen before spreading to organs in the body. (Weldon
School of Biomedical Engineering, Purdue University)
A publication-quality photo is available at
http://news.uns.purdue.edu/images/+2009/cheng-fatcancer.jpg
