title: Imaging the microenvironment of pancreatic cancer patient-derived orthotopic xenografts (PDOX) growing in transgenic nude mice expressing GFP, RFP, or CFP.
abstract: We have developed a multi-color, imageable, orthotopic mouse model for individual patients with pancreatic cancer. The tumors are labeled by first passaging them orthotopically through transgenic nude mice expressing green fluorescent protein (GFP), red fluorescent protein (RFP), or cyan fluorescent protein (CFP). Passage of the tumors in these colored transgenic mice labels the stromal cells of the tumor. The cancer cells in the PDOX are labeled in situ with GFP by telomerase-dependent adenovirus OBP-401. The models are termed imageable patient-derived orthotopic xenografts (iPDOX). The tumors acquired brightly-fluorescent stromal cells from the transgenic host mice, which were stably associated with the tumors through multiple passages. The colored fluorescent protein-expressing stromal cells included cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). This model enables powerful color-coded imaging of the interaction of cancer and stromal cells during tumor progression and treatment.
authors.affiliation: AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA. Electronic address: all@anticancer.com.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.affiliation: Department of Surgery, University of California, San Diego, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
mesh_terms: D000818:Animals; D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D049452:Green Fluorescent Proteins / Q000096:biosynthesis* / Q000235:genetics; D064593:Heterografts; D006801:Humans; D008164:Luminescent Proteins / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008819:Mice, Nude; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D061848:Optical Imaging; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment; D000097573:Red Fluorescent Protein
chemical_list: D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein; C485182:Cyan Fluorescent Protein
keywords: Cyan fluorescent protein; Green fluorescent protein; Nude mice; Patient-derived orthotopic xenografts (PDOX); Red fluorescent protein; Tumor microenvironment