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First steps in the formation of pancreatic cancer identified

4 December 2014

Researchers at the Mayo Clinic in the USA have identified first steps in the origin of pancreatic cancer and believe their findings suggest ways to prevent cancer developing.

In a study published in the journal Cancer Discovery, the scientists describe the molecular steps necessary for the cells that release digestive enzymes in the pancreas - called acinar cells - to become precancerous lesions. Some of these lesions can then develop into cancer.

"If we understand how these lesions come about, we may be able to stop the cancer train altogether," says cancer biologist Dr Peter Storz, who led the research.

The scientists studied pancreatic cells with mutations in the Kras gene.  Kras produces a protein that regulates cell division, and the gene is mutated in many cancers. More than 95 per cent of pancreatic cancer cases are found to have a Kras mutation.

The researchers detailed the steps that led acinar cells with Kras mutations to change 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 trigger the expression of a molecule called 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 drives the initiation of pancreatic cancer," Dr Storz says, adding that the process can be stopped when testing on mice.  

 "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," he explains.  "Doing either one reduced the number of precancerous lesions."

Dr Storz also said that that a ‘neutralizing antibody’ that blocks ICAM-1has already been developed and is being tested for range 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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