Jefferson Scientists’ Discovery May Help Explain Smoking-Pancreatic Cancer Link
If
lung cancer and heart disease aren’t bad enough, cigarette smokers are
also at higher risk for developing, among other things, pancreatic
cancer. Now, researchers at the Kimmel Cancer Center at Jefferson in
Philadelphia have preliminary evidence indicating one possible reason
why. Data being presented April 13, 2008 during the Annual Meeting of
the American Association for Cancer Research shows that they have found
that nicotine in cigarettes increases the production of a protein that
is known to promote cancer cell survival, invasion and spread.
According
to Hwyda Arafat, M.D., Ph.D., associate professor of Surgery at
Jefferson Medical College of Thomas Jefferson University, the protein,
osteopontin, is found in a variety of fluids in the body, such as
plasma, cerebrospinal fluid, synovial fluid and breast milk.
Osteopontin is also present in different organs and plays an important
role during embryonic development. Recent studies have demonstrated
that osteopontin levels are significantly higher in the blood and
pancreas tissue of pancreatic cancer patients. The protein, when
over-produced, can make cancer cells more likely to become metastatic.
Dr.
Arafat wanted to see if osteopontin might play a role in the cigarette
smoking-pancreatic cancer connection. In collaboration with groups at
the University of Nebraska and Rutgers University, Dr. Arafat and her
co-workers looked at rats exposed to cigarette smoke and measured the
amount of osteopontin in the rat pancreas and blood. They found that
the more cigarette smoke to which the rats were exposed, the greater
the amount of nicotine in the blood and osteopontin in the pancreas.
The
researchers also looked at osteopontin expression in pancreatic cancer
cell lines exposed to nicotine, finding that osteopontin expression
went up when the cells were exposed to more nicotine. “We found that
dose-dependently, nicotine increased osteopontin expression not only
through transcriptional but also translational (protein secretion)
levels in pancreatic cancer cells,” Dr. Arafat explains. Pancreas
tissue samples from pancreatic cancer patients also showed higher than
normal levels of the protein.
Dr.
Arafat believes that osteopontin could be a drug target. “We are now
proposing that perhaps blocking osteopontin can interfere with the
progression of pancreatic cancer and other cancers,” she says, adding
that her team would like to understand more about osteopontin’s effects
on pancreatic cancer cell behavior. Dr. Arafat’s group now is comparing
differences in osteopontin expression between smokers and non-smokers.
“For example, if you put the cells with nicotine and block osteopontin, will the cells still be migratory? Is it osteopontin
or something else in combination that is at work here?”
Pancreatic
cancer, the fourth-leading cause of cancer death in this country, takes
some 34,000 lives a year. The disease is difficult to treat; it
frequently is detected after it has spread. Only 4 percent of
individuals with pancreatic cancer live for five years after diagnosis,
and about 25 percent of those who undergo successful surgical removal
of their disease live at least that long.
Media Only Contact:
Steve Benowitz
Thomas Jefferson University Hospital
Phone: (215) 955-6300
Published: 4/13/2008