PANCREATIC CANCER MODELS
Modeling Pancreatic Cancer in the Laboratory
In order for researchers to make progress studying pancreatic cancer, they need strategies to model the disease in the laboratory setting. The most commonly used tools to study pancreatic cancer are cell lines, xenograft mouse models, and genetically engineered mice. Please see descriptions of each below:
Pancreatic cancer cell lines are derived from patient tumor samples, often obtained from surgical resection of earlier-stage disease. Upon surgical removal of a patient’s tumor, pieces of tissue are brought into the laboratory, broken down into individual cells, and grown on a plastic dish. Researchers can maintain these cultures of living cells indefinitely, and perform experiments investigating the cells’ response to various stimuli or inhibitors (drugs), measure cellular growth and death rate, and analyze other features. Moreover, these cells can be genetically manipulated to over-express or down-regulate particular genes/proteins of interest to the researcher, leading to measurable changes in cellular behavior. Advantages to this strategy include access to unlimited supply of cells, speed of experiments, and low cost. The major disadvantage is the fact that cellular behavior in a dish cannot fully recapitulate that of cells found in the body, including interaction with other tissue types and context among other bodily functions.
Xenograft mouse model
A way to combine cell line experimentation with a live animal model is a process known as xenografting. A xenograft involves pancreatic cancer cells (either from a cell line or directly from a human patient’s tumor specimen) being injected into a mouse. The cells can be injected directly into a mouse pancreas. Within a few weeks, the cells grow into a mass, recapitulating a tumor. Cells that have been genetically manipulated can be xenografted into mice, allowing for analyses of rate of tumor growth, responsiveness to various drugs, and time to disease progression. A downside is that anytime mouse experiments are conducted, there is a significantly higher expense than studying cells in a dish. Further, because human cells are being artificially implanted inside a mouse, the tumors do not grow exactly as a naturally-occurring human or mouse tumor might.
Genetically engineered mouse model
The last major strategy to studying pancreatic cancer in the laboratory involves genetically engineered mouse models. Success with this technique in pancreatic cancer was first achieved by David Tuveson, MD, PhD, while his research was funded by the 2003 Pancreatic Cancer Action Network – AACR Career Development Award. Dr. Tuveson and colleagues were able to generate mice that have crucial genetic changes specific to the tissue of the pancreas. These mice then develop pancreatic cancer over a period of several months. A significant advantage of this model is that the initiation and progression of pancreatic cancer in these mice closely mimics human disease, allowing clinically relevant evaluation of potential therapies or methods for early detection. Disadvantages of this model include cost and time necessary for the mouse to develop tumors. Further, any additional genetic manipulations of the mouse could be extremely complex and time-consuming.
Researchers who study pancreatic cancer may choose any single or combination of methods to model the disease in the laboratory. Each technique has advantages and disadvantages, and it is important to choose the appropriate model(s) to answer the investigator’s specific research questions.