Generating a pancreatic cancer mouse model: from Cancer Stem Cells to in vivo imaging strategies

Background: Pancreatic cancer remains a highly aggressive and not curable cancer in spite of the ample research in the last decades. Since conventional treatment approaches have not satisfactory effects because they don’t result in a significant improvement of the disease outcome, an effective research system is still strongly needed, in order to accurately predict the clinical efficacy of novel compounds developed for pancreatic cancer treatment. Aim: the aim of the current study is to contribute to the generation of a complete and straightforward system useful for the identification and pre-clinic screening of novel drug for the treatment pancreatic cancer. This system should provide the techniques, the protocols and a pancreatic cancer model suitable firstly for in vitro high-throughput compounds screening and then for in vivo validation of the selected molecules. Results: findings previously obtained in our laboratory have already demonstrate potential stemlike behavior of Panc-1 cells growing as 3-dimensional spheres (Panc1-spheres), isolated from adherent Panc-1 cell line. In this study we continued with the in vivo characterization of Panc-1 spheres because we used them as pancreatic cancer cell line model in the compounds screening system we are generating. So, we performed subcutaneus and orthotopical injections in nude mice with adherent Panc1 and Panc1-spheres cells. Tumor growths were followed using MRI. In order to deepen the characterization of Panc1-spheres, we also studied EMT on tumors derived from this experiment such as in vitro in both cell lines. Moreover, we observed that an improvement of imaging strategies was actually needed, in order to better control above all the formation of small masses as metastasis and early primary tumors, since MRI was not sufficient when used alone. For this reason, we also decided to focus our attention to the most important non-invasive small animalimaging modalities available today, in particular MRI, Micro-Ultrasound (US) and In Vivo Optical Imaging. Then, we correlated these techniques, arriving to the point to have an “imaging protocol”, able to offset some of the limitation of each modality when used alone, to be used in the compounds screening system we would like to generate. Conclusion: Our findings have demonstrated that the pancreatic cancer spheres are more than just cancer stem-like cells. Our mouse model, established with Sphere-growing cells, may be used for the testing of novel compounds specifically designed to target this stem-like compartment, resistant to standard chemotherapies. A combined imaging approach, with combine MRI, Optical imaging and US, in this contest become extremely important, in order to follow primary tumor sizes and metastasis detection before and after the treatment with novel compounds.