title: Multi-color palette of fluorescent proteins for imaging the tumor microenvironment of orthotopic tumorgraft mouse models of clinical pancreatic cancer specimens.
abstract: Pancreatic-cancer-patient tumor specimens were initially established subcutaneously in NOD/SCID mice immediately after surgery. The patient tumors were then harvested from NOD/SCID mice and passaged orthotopically in transgenic nude mice ubiquitously expressing red fluorescent protein (RFP). The primary patient tumors acquired RFP-expressing stroma. The RFP-expressing stroma included cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). Further passage to transgenic nude mice ubiquitously expressing green fluorescent protein (GFP) resulted in tumors that acquired GFP stroma in addition to their RFP stroma, including CAFs and TAMs as well as blood vessels. The RFP stroma persisted in the tumors growing in the GFP mice. Further passage to transgenic nude mice ubiquitously expressing cyan fluorescent protein (CFP) resulted in tumors acquiring CFP stroma in addition to persisting RFP and GFP stroma, including RFP- and GFP-expressing CAFs, TAMs and blood vessels. This model can be used to image progression of patient pancreatic tumors and to visually target stroma as well as cancer cells and to individualize patient therapy.
authors.affiliation: AntiCancer, Inc., San Diego, California 92111, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suetsugu
authors.forename: Matthew
authors.initials: M
authors.lastname: Katz
authors.forename: Jason
authors.initials: J
authors.lastname: Fleming
authors.forename: Mark
authors.initials: M
authors.lastname: Truty
authors.forename: Ryan
authors.initials: R
authors.lastname: Thomas
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.forename: Shigetoyo
authors.initials: S
authors.lastname: Saji
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D018450:Disease Progression; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006801:Humans; D008164:Luminescent Proteins / Q000096:biosynthesis; D008264:Macrophages; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment; D000097573:Red Fluorescent Protein
chemical_list: D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein; C485182:Cyan Fluorescent Protein