Metastasis of pancreatic cancer in action

Ben Stanger, MD, PhD, assistant professor of Medicine in the Division of Gastroenterology at the Perelman School of Medicine, University of Pennsylvania, and Andrew Rhim, MD, a Gastroenterology Fellow in the Stanger lab, discovered that pancreatic cancer cells in an animal model begin to spread before clinically obvious tumor tissue is detected. What's more, they showed that inflammation enhances cancer progression in part by facilitating a cellular transformation that leads to entry of cancer cells into the circulation. They report their findings this week in Cell.

Metastasis has been difficult to study because it involves a series of unpredictable events. To capture these events, the team developed a sensitive method to tag and track pancreatic epithelial cells in a mouse model of pancreatic cancer. Tagged cells invaded and entered the bloodstream unexpectedly early, before overt malignancy could be detected by rigorous analysis of tissue slides.

Pancreatic cancer is among the most lethal of cancers, with no real treatments, and at the time of diagnosis up to three-quarters of patients have metastatic disease, says Stanger. Little is known about how pancreatic cancer cells spread, "What leads to this are rare events that are hard to catch in tissues. Small numbers of cells break off tumors and move, but how can we find them?"

These wandering cells are associated with a phenomenon called the epithelial-to-mesenchymal transition (EMT).

This change in cell motility is an important process during the development of embryos. But when the transition is aberrantly reactivated in adults it can have dire physiological consequences, leading to cancer metastasis as well as other disease processes. Epithelial cells form a covering or lining of a body surface and are the type of cell from which most solid tumors arise. However, when a molecular switch is turned off or absent, epithelial cells acquire characteristics of another cell type, called mesenchymal cells, and gain the ability to migrate and move away from the primary tumor site.

Using a mouse model of pancreatic cancer developed at Penn in 2005, the team delivered mutations in an oncogene and a tumor suppressor protein, K-ras and p53 respectively, in the pancreas. A green marker was also induced in the embryos' still-forming pancreas. At about one to two months, the juvenile mice developed pre-malignant lesions, and at about four to five months full blown pancreatic cancer.

Metastatic pancreatic cancer is the term used to describe the spread of the cancer to a distant organ. Unlike normal cells, cancer cells have the power to attack other organs directly or to spread via lymphatic channels and the blood stream to other areas of the body. This is called metastasis.

As cells keep on to growing uncontrollably, they form a pancreatic mass or tumor. These cells can suspend the normal function of the system or organ by smothering and killing the normal cells or by blocking the passageway from one organ to another.