Establishment of an orthotopic pancreatic cancer mouse model: cells suspended and injected in Matrigel.

AIM: To establish an orthotopic mouse model of pancreatic cancer that mimics the pathological features of exocrine pancreatic adenocarcinoma. METHODS: Pan02 cells were suspended in low-temperature Matrigel and injected into the parenchyma of pancreatic tails of C57BL/6 mice, with cells suspended in phosphate buffered saline (PBS) serving as a control. Primary and implanted tumors were confirmed pathologically. The rate of tumor formation and intraperitoneal implantation in the two groups were compared at different time points after injection. Leakage and intra-abdominal dispersion of Matrigel and PBS, both dyed with methylene blue, were compared after injection into the parenchyma of the pancreas. We observed adherence and proliferation in Pan02 cells suspended in Matrigel in vitro. We also compared the pathological manifestation of this orthotopic pancreatic cancer model in the head and tails of the pancreas. The characteristics of the origin of epithelial cells and exocrine markers of established orthotopic pancreatic tumors were confirmed using immunohistochemistry. RESULTS: Diluted Matrigel could form a gel drip in the pancreatic parenchyma, effectively preventing leakage from the injection site and avoiding dispersion in the abdominal cavity. Pan02 cells were able to adhere to a dish, proliferate, and migrate in the gel drip. The tumor formation rate in the Matrigel group was 100% at both 2 and 3 wk after injection, whereas it was 25.0% and 37.5% in the PBS group at 2 and 3 wk, respectively (P < 0.05). The intraperitoneal tumor implantation rate was 75.0% in the PBS group after 3 wk of injection, while it was 12.5% in the Matrigel group (P < 0.05). Hepatoduodenal ligament and duodenal invasions with obstructive jaundice and upper digestive obstruction with mesenteric lymph node metastasis were observed in the pancreatic head group. In the pancreatic tail group, spleen and gastric invasion were dominant, leading to retroperitoneal lymph nodes metastasis. Positive immunohistochemical staining of cytokeratin and negative staining of vimentin and chromogranin A confirmed that the orthotopic pancreatic tumor injected with Pan02 cells suspended in Matrigel was of epithelial origin and expressed exocrine markers of cancer. CONCLUSION: This method of low-temperature Matrigel suspension and injection is effective for establishing an orthotopic mouse model of pancreatic cancer.

Emerging inorganic nanomaterials for pancreatic cancer diagnosis and treatment.

Pancreatic cancer is a devastating disease with incidence increasing at an alarming rate and survival not improved substantially during the past three decades. Although enormous efforts have been made in early detection and comprehensive treatment for this disease, little or no survival improvement was obtained, which necessitates the development of novel strategies. Emerging inorganic nanomaterials, such as carbon nanotubes, quantum dots, mesoporous silica/gold/supermagnetic nanoparticles, have been widely used in biomedical research with great optimism for cancer diagnosis and therapy. Such nanoparticles possess unique optical, electrical, magnetic and/or electrochemical properties. With such properties along with their impressive nano-size, these particles can be targeted to cancer cells, tissues, and ligands efficiently and monitored with extreme precision in real-time. In additional to liposome, dendrimer, and polymeric nanoparticles, they are considered the most promising nanomaterials with the capability of both cancer detection and multimodality treatment. Emerging approaches to harness nanotechnology to optimize the existing diagnostic and therapeutic tools for pancreatic cancer have been extensively explored during the recent years. Future options for early detection, individual therapy and monitoring responses of pancreatic cancer are focused on multifunctional nanomedicine. In this review, we present the recent development of clinically applicable inorganic nanoparticles, with focus on the diagnosis and treatment of pancreatic cancer. Furthermore, their advantages in theranostic nanomedicine, and challenges of translation to clinical practice, are discussed.