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First steps in formation of pancreatic cancer identified

Date: November 10, 2014

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Source: Mayo Clinic

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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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Shown is a region of a pancreas with preneoplastic lesions. Red labeling indicates
macrophages, green labeling indicates pancreatic acinar cells that dedifferentiate,
and grey labeling indicates further progressed pancreatic lesions.
Credit: Image courtesy of Mayo Clinic

[Click to enlarge image]

esearchers at Mayo Clinic's campus in Jacksonville say they have

identified first steps in the origin of pancreatic cancer and that their
findings suggest preventive strategies to explore.

In an online issue of Cancer Discovery, 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.
"Pancreatic cancer develops from these lesions, so if
we understand how these lesions come about, we may
be able to stop the cancer train altogether," says the
study's lead investigator, Peter Storz, Ph.D., a cancer
biologist.

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The need for new treatment and prevention strategies is

pressing, Dr. Storz says. Pancreatic cancer is one of the most aggressive human
cancers -- symptoms do not occur until the cancer is well advanced. One-year survival
after diagnosis is only 20 percent. It is the fourth leading cause of cancer death in this

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Origin of Inflammation-Driven Pancreatic

Cancer Decoded
Aug. 5, 2013 Researchers have revealed the
process by which chronic inflammation of the
pancreas, pancreatitis, morphs into pancreatic
cancer. They say their findings point to ways to
identify pancreatitis ... full story

Study Sheds Light on How Pancreatic

Cancer Begins
Nov. 29, 2012 Scientists examined the tumorinitiating events leading to pancreatic cancer (also
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Link Between Inflammation and Pancreatic

Cancer Discovered
Apr. 11, 2011 Solving part of a medical mystery,
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Malignancy and Survival in Patients With

Pancreatic Disease

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."

May 3, 2010 Quality-of-life measures used

routinely to assess treatment outcomes for patients
with pancreatic disease may be used to predict
both malignancy and survival for those patients,
according to a new ... full story
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Tissue cDNA Array

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.

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Story Source:

Health & Medicine

The above story is based on materials provided by Mayo Clinic. Note: Materials may
be edited for content and length.

Body Weight Heavily Influenced by Gut Microbes:

Genes Shape Body Weight by Affecting Gut
Microbes

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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Mayo Clinic. "First steps in formation of pancreatic cancer identified."

ScienceDaily. ScienceDaily, 10 November 2014.
<www.sciencedaily.com/releases/2014/11/141110110106.htm>.

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