Clinically-relevent orthotopic metastatic models of pancreatic cancer imageable with fluorescent genetic reporters.

This article describes authors' cumulative experience with the development and preclinical application of clinically-relevant, metastatic orthotopic mouse models of pancreatic cancer made imageable with genetic reporters. These models utilize the human pancreatic cancer cell lines which have been genetically engineered to selectively express high levels of green fluorescent protein (GFP) or red fluorescent protein (RFP). Tumors with fluorescent genetic reporters are established subcutaneously in nude mice, and fragments of the subcutaneous tumors are then surgically transplanted onto the pancreas. Loco-regional tumor growth and distant metastasis of these orthotopic implants occurs spontaneously and rapidly throughout the abdo-men in a manner consistent with clinical human disease. Highly specific, high-resolution, real-time quantitative fluorescence imaging of tumor growth and metastasis may be achieved in vivo without the need for contrast agents, invasive techniques, or expensive imaging equipment. A high correlation between florescence optical imaging, magnetic resonance imaging, and ultrasound in these models has been demonstrated. Transplantation of RFP-expressing tumor fragments onto the pancreas of GFP- or cyan fluorescent protein-expressing transgenic mice was used to facilitate visualization of tumor-host interaction between the pancreatic cancer cells and host-derived stroma and vasculature. Such in vivo models have enabled visualization in real time and acquisition of images of the progression of pancreatic cancer in the live animal, the models also demonstrate the real-time antitumor and antimetastatic effects of several novel therapeutic strategies on pancreatic malignancy. These fluorescent models are therefore powerful and reliable tools with which to investigate metastatic human pancreatic cancer and novel therapeutic strategies directed against it.