title: Patient-derived xenograft models for pancreatic adenocarcinoma demonstrate retention of tumor morphology through incorporation of murine stromal elements.
abstract: Direct implantation of viable surgical specimens provides a representative preclinical platform in pancreatic adenocarcinoma. Patient-derived xenografts consistently demonstrate retained tumor morphology and genetic stability. However, the evolution of the tumor microenvironment over time remains poorly characterized in these models. This work specifically addresses the recruitment and incorporation of murine stromal elements into expanding patient-derived pancreatic adenocarcinoma xenografts, establishing the integration of murine cells into networks of invading cancer cells. In addition, we provide methods and observations in the establishment and maintenance of a patient-derived pancreatic adenocarcinoma xenograft model. A total of 25 histologically confirmed pancreatic adenocarcinoma specimens were implanted subcutaneously into nonobese diabetic severe combined immunodeficiency mice. Patient demographics, staging, pathological analysis, and outcomes were analyzed. After successful engraftment of tumors, histological and immunofluorescence analyses were performed on explanted tumors. Pancreatic adenocarcinoma specimens were successfully engrafted in 15 (60%) of 25 attempts. Successful engraftment does not appear to correlate with clinicopathologic factors or patient survival. Tumor morphology is conserved through multiple passages, and tumors retain metastatic potential. Interestingly, despite morphological similarity between passages, human stromal elements do not appear to expand with invading cancer cells. Rather, desmoplastic murine stroma dominates the xenograft microenvironment after the initial implantation. Recruitment of stromal elements in this manner to support and maintain tumor growth represents a novel avenue for investigation into tumor-stromal interactions.
authors.affiliation: Department of Surgery, Colleges of Medicine, Dentistry, and Public Health and Health Professions, University of Florida Health Science Center, Gainesville, Florida.
authors.forename: Daniel
authors.initials: D
authors.lastname: Delitto
authors.affiliation: Department of Pathology, Colleges of Medicine, Dentistry, and Public Health and Health Professions, University of Florida Health Science Center, Gainesville, Florida.
authors.forename: Kien
authors.initials: K
authors.lastname: Pham
authors.affiliation: Department of Surgery, Colleges of Medicine, Dentistry, and Public Health and Health Professions, University of Florida Health Science Center, Gainesville, Florida.
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Vlada
authors.affiliation: Department of Surgery, Colleges of Medicine, Dentistry, and Public Health and Health Professions, University of Florida Health Science Center, Gainesville, Florida; North Florida/South Georgia Veterans Health System, Colleges of Medicine, Dentistry, and Public Health and Health Professions, University of Florida Health Science Center, Gainesville, Florida.
authors.forename: George A
authors.initials: GA
authors.lastname: Sarosi
authors.affiliation: Department of Surgery, Colleges of Medicine, Dentistry, and Public Health and Health Professions, University of Florida Health Science Center, Gainesville, Florida; North Florida/South Georgia Veterans Health System, Colleges of Medicine, Dentistry, and Public Health and Health Professions, University of Florida Health Science Center, Gainesville, Florida.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Thomas
authors.affiliation: Department of Surgery, Colleges of Medicine, Dentistry, and Public Health and Health Professions, University of Florida Health Science Center, Gainesville, Florida.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Behrns
authors.affiliation: Department of Pathology, Colleges of Medicine, Dentistry, and Public Health and Health Professions, University of Florida Health Science Center, Gainesville, Florida.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Surgery, Colleges of Medicine, Dentistry, and Public Health and Health Professions, University of Florida Health Science Center, Gainesville, Florida.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hughes
authors.affiliation: Department of Periodontology and Oral Biology, Colleges of Medicine, Dentistry, and Public Health and Health Professions, University of Florida Health Science Center, Gainesville, Florida.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Wallet
authors.affiliation: Department of Surgery, Colleges of Medicine, Dentistry, and Public Health and Health Professions, University of Florida Health Science Center, Gainesville, Florida. Electronic address: jose.trevino@surgery.ufl.edu.
authors.forename: Jose G
authors.initials: JG
authors.lastname: Trevino
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D064593:Heterografts; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D010190:Pancreatic Neoplasms / Q000473:pathology*; D014183:Transplantation, Heterologous / Q000379:methods*; D059016:Tumor Microenvironment