Abstract
Mice have been employed as models of cancer for over a century, providing significant advances in our understanding of this multifaceted family of diseases. In particular, orthotopic tumor xenograft mouse models are emerging as the preference for cancer research due to increased clinical relevance over subcutaneous mouse models. In the current study, we developed orthotopic pancreatic cancer xenograft models in mice by a minimally invasive method, ultrasound guided injection (USGI) comparable to highly invasive surgical orthotopic injection (SOI) methods. This optimized method prevented injection complications such as recoil of cells through the injection canal or leakage of cells out of the pancreas into the peritoneal cavity. Tumor growth was monitored in vivo and quantified by ultrasound imaging weekly, tumors were also detected by in vivo fluorescence imaging using a tumor targeted molecular probe. The mean tumor volumes for the USGI and SOI models after 2 weeks of tumor growth were 205 mm3 and 178 mm3 respectively. By USGI of human pancreatic cancer cell lines, human orthotopic pancreatic cancer xenografts were established. Based on ultrasound imaging, the orthotopic human pancreatic cancer xenograft take rate was 100% for both human pancreatic cancer cell lines used, MiaPaCa-2 and Su86.86, with mean tumor volumes of 28 mm3and 30 mm3. We demonstrated that this USGI method is feasible, reproducible, facile, minimally invasive and improved compared to the highly-invasive SOI method for establishing orthotopic pancreatic tumor xenograft models suitable for molecular imaging.
Highlights
Mice have been employed as models of cancer for over a century, providing significant advances in our understanding of this multifaceted family of diseases
We investigated the feasibility of developing orthotopic human pancreatic cancer xenograft models using ultrasound guided injection (USGI) of tumor cells
To the best of our knowledge, this is the first account of orthotopic xenografting of human pancreatic cancer cells by USGI into the mouse pancreas
Summary
Mice have been employed as models of cancer for over a century, providing significant advances in our understanding of this multifaceted family of diseases. There are currently four main areas of cancer research that use mouse models: basic biology and physiology, experimental therapeutics, prevention, and genetics susceptibility and risk. These models have proven to be useful in validation of gene function, characterization of novel cancer genes and tumor biomarkers, gaining insight into the molecular and cellular mechanisms underlying tumor initiation and multistage processes of tumorigenesis, and providing better clinical models in which to test novel therapeutic strategies [1]. Tumor xenograft mouse models are commonly used in preclinical studies. There are several key advantages of using human tumor xenografts: they feature the complexity of genetic and epigenetic abnormalities that exist in the human tumor population; can be used to aid in the development of individualized molecular therapeutic approaches; and can be implanted orthotopically to reproduce the organ environment in which the tumor grows, so that the effect of the tumor on its microenvironment can be modulated [3]
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