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Summary: The first steps in the origin of pancreatic cancer have been identified by
researchers who say that their findings suggest preventive strategies to
explore. The scientists described the molecular steps necessary for
acinar cells in the pancreas -- the cells that release digestive enzymes - to become precancerous lesions. Some of these lesions can then
morph into cancer.
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country.
The scientists studied pancreatic cells with Kras genetic mutations. Kras produces a
protein that regulates cell division, and the gene is often mutated in many cancers.
More than 95 percent of pancreatic cancer cases have a Kras mutation.
The researchers detailed the steps that led acinar cells with Kras mutations to
transform into duct-like cells with stem cell-like properties. Stem cells, which can
divide at will, are also often implicated in cancer.
They found that Kras proteins in the acinar cells induce the expression of a molecule,
ICAM-1, which attracts macrophages, a specific kind of immune cells. These
inflammatory macrophages release a variety of proteins, including some that loosen
the structure of the cells, allowing acinar cells to morph into different types of cells.
These steps produced the precancerous pancreatic lesions.
"We show a direct link between Kras mutations and the inflammatory environment that
drive the initiation of pancreatic cancer," Dr. Storz says.
But the process can be halted in laboratory mice, he adds. "We could do this two
ways -- by depleting the macrophages or by treating the transformed cells with a
blocking antibody that shuts down ICAM-1," says Dr. Storz. "Doing either one reduced
the number of precancerous lesions."
Pancreatic Cancer
Signs
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Dr. Storz noted that a neutralizing antibody that blocks ICAM-1has already been
developed. It is being tested for a wide variety of disorders, including stroke and
rheumatoid arthritis.
"Understanding the crosstalk between acinar cells with Kras mutations and the
microenvironment of those cells is key to developing targeted strategies to prevent and
treat this cancer," he says.
Story Source:
The above story is based on materials provided by Mayo Clinic. Note: Materials may
be edited for content and length.
Journal Reference:
1. G.-Y. Liou, H. Doppler, B. Necela, B. Edenfield, L. Zhang, D. W. Dawson, P. Storz.
Mutant Kras-induced expression of ICAM-1 in pancreatic acinar cells causes
attraction of macrophages to expedite the formation of precancerous
lesions.. Cancer Discovery, 2014; DOI: 10.1158/2159-8290.CD-14-0474
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Pancreatic Cancer
Signs
How To Tell If You Have
Pancreatic Cancer. Symptoms,
Causes, & More.
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