STRESS MAY HASTEN THE GROWTH OF MELANOMA TUMORS BUT COMMON BETA-BLOCKER MEDICATIONS MIGHT SLOW THAT PROGRESS
COLUMBUS,
Ohio – For patients with a particularly aggressive form of skin cancer
– malignant melanoma – stress, including that which comes from simply
hearing that diagnosis, might amplify the progression of their disease.
But
the same new research that infers this also suggests that the use of
commonly prescribed blood pressure medicines might slow the development
of those tumors and therefore improve these patients’ quality of life.
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Eric Yang |
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Ronald Glaser |
The
study, the third by Ohio State University scientists in the last two
years that looked for links between stress hormones and diseases like
cancer, is published in the the journal Brain, Behavior and Immunity.
Eric
V. Yang, a research scientist at the Institute for Behavioral Medicine
Research (IBMR), exposed samples of three melanoma cell lines to the
compound norepinephrine, a naturally occurring catecholamine that
functions as a stress hormone. In times of increased stress, levels of
norepinephrine increase in the bloodstream.
Yang and
colleague Ronald Glaser were looking for changes in the levels of three
proteins released by the cells. Glaser is a professor of molecular
virology, immunology and medical genetics, member of the university’s
Comprehensive Cancer Center and director of the IBMR.
One
of the proteins – vascular endothelial growth factor, or VEGF – plays a
key role in stimulating the growth of new blood vessels needed to feed
a growing tumor, a process called angiogenesis. The other two
proteins, Interleukin-6 and Interleukin-8, are both involved in
fostering tumor growth.
All three of the cell lines were
grown from tissues taken from secondary tumors that had metastasized
from a primary site and they signify aggressive forms of cancer. But
one of them – C8161 – represented the most aggressive and advanced form
of melanoma.
“We noticed that all three of these proteins
increased in response to the norepinephrine,” Yang explained, adding
that in the C8161 cells, “we got a 2,000 percent increase in IL-6. In
untreated samples from this cell line, you normally can’t detect any
IL-6 at all.
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The
research is showing not only that different forms of cancer react
differently to stress hormones but also that those reactions can vary
within a specific form of the disease, with the possibility of a more
aggressive form of the disease reacting more strongly to the stressors.
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“What
this tells us is that stress might have a worse effect on melanoma that
is in a very aggressive or advanced stage, and that one marker for that
might be increased levels of IL-6,” he said.
The
researchers ruled out cell proliferation – an increase in the number of
cells present – as a reason for the increase in all three proteins.
That meant that the only other answer was that the cells were
increasing their expression of the genes responsible for producing
these compounds.
The researchers showed that the
norepinephrine molecule binds to receptors on the surface of cancer
cells and once this linkage occurs, it stimulates the release of the
proteins that support angiogenesis and tumor growth.
Yang
and Glaser first confirmed that the receptors were present on cells in
all three cell lines and then tested what would happen when the
receptors were blocked by common blood pressure medicine – the
so-called “beta-blockers.”
When the beta-blockers did
bind to the receptors, the production of the three proteins reduced
significantly, suggesting that in patients with melanoma, using these
types of medications might be used to slow the progression of the
disease in patients.
While the study was restricted to
tumor cell lines, rather than using animal models or human patients,
the findings are still exciting. The researchers found strong evidence
that the same receptors are expressed on the surface of tumor cells
from biopsies that were taken from melanoma patients. That supports
the clinical importance of the results.
Two earlier
studies on different tumor cell lines – one prepared from a multiple
myeloma and the other from a nasopharyngeal carcinoma – also showed
that exposure to norepinephrine increased the levels of proteins
responsible for accelerating tumor growth.
The research
is showing not only that different forms of cancer react differently to
stress hormones but also that those reactions can vary within a
specific form of the disease, with the possibility of a more aggressive
form of the disease reacting more strongly to the stressors.
For
melanoma patients, that can be very important since these tumors are
able to metastasize, or spread, when they are much smaller than most
other solid cancers. The American Cancer Society estimates that nearly
48,000 cases of melanoma are diagnosed each year and nearly 8,000
people are killed each year by the disease.
This research
was supported in part by the National Cancer Institute. Other
collaborators in the study included Sanford Barsky, professor and chair
of pathology; and IBMR members Elise Donovan, Min Chen, Amy Gross,
Jeanette Webster Marketon and Seung-jae Kim.
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Contact: Eric V. Yang, (614) 292-0364; yang.3@osu.edu or Ronald Glaser, (614) 292-5526; glaser.1@osu.edu.
Written by Earle Holland, (614) 292-8384; holland.8@osu.edu.
