title: A Novel Immunocompetent Mouse Model of Pancreatic Cancer with Robust Stroma: a Valuable Tool for Preclinical Evaluation of New Therapies.
abstract: A valid preclinical tumor model should recapitulate the tumor microenvironment. Immune and stromal components are absent in immunodeficient models of pancreatic cancer. While these components are present in genetically engineered models such as Kras(G12D); Trp53(R172H); Pdx-1Cre (KPC), immense variability in development of invasive disease makes them unsuitable for evaluation of novel therapies. We have generated a novel mouse model of pancreatic cancer by implanting tumor fragments from KPC mice into the pancreas of wild type mice. Three-millimeter tumor pieces from KPC mice were implanted into the pancreas of C57BL/6J mice. Four to eight weeks later, tumors were harvested, and stromal and immune components were evaluated. The efficacy of Minnelide, a novel compound which has been shown to be effective against pancreatic cancer in a number of preclinical murine models, was evaluated. In our model, consistent tumor growth and metastases were observed. Tumors demonstrated intense desmoplasia and leukocytic infiltration which was comparable to that in the genetically engineered KPC model and significantly more than that observed in KPC tumor-derived cell line implantation model. Minnelide treatment resulted in a significant decrease in the tumor weight and volume. This novel model demonstrates a consistent growth rate and tumor-associated mortality and recapitulates the tumor microenvironment. This convenient model is a valuable tool to evaluate novel therapies.
authors.affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Kaustav
authors.initials: K
authors.lastname: Majumder
authors.affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Nivedita
authors.initials: N
authors.lastname: Arora
authors.affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Shrey
authors.initials: S
authors.lastname: Modi
authors.affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Chugh
authors.affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Nomura
authors.affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Bhuwan
authors.initials: B
authors.lastname: Giri
authors.affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Rajinder
authors.initials: R
authors.lastname: Dawra
authors.affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Sundaram
authors.initials: S
authors.lastname: Ramakrishnan
authors.affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Sulagna
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Saluja
authors.affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA. dudej001@umn.edu.
authors.forename: Vikas
authors.initials: V
authors.lastname: Dudeja
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004224:Diterpenes; D004852:Epoxy Compounds; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D010755:Organophosphates / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D010616:Phenanthrenes / Q000627:therapeutic use; D011897:Random Allocation; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D004852:Epoxy Compounds; D010755:Organophosphates; D010616:Phenanthrenes; C579022:14-O-phosphonooxymethyltriptolide disodium salt
keywords: Immunocompetent mouse model; Pancreatic cancer; Stroma; Syngeneic