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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.
AuthorsAtsushi Suetsugu, Matthew Katz, Jason Fleming, Mark Truty, Ryan Thomas, Hisataka Moriwaki, Michael Bouvet, Shigetoyo Saji, Robert M Hoffman
JournalJournal of cellular biochemistry (J Cell Biochem) Vol. 113 Issue 7 Pg. 2290-5 (Jul 2012) ISSN: 1097-4644 [Electronic] United States
PMID22573550 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2012 Wiley Periodicals, Inc.
Chemical References
  • Cyan Fluorescent Protein
  • Fluorescent Dyes
  • Luminescent Proteins
  • red fluorescent protein
  • Green Fluorescent Proteins
Topics
  • Animals
  • Diagnostic Imaging (methods)
  • Disease Models, Animal
  • Disease Progression
  • Fluorescent Dyes
  • Green Fluorescent Proteins (biosynthesis)
  • Humans
  • Luminescent Proteins (biosynthesis)
  • Macrophages
  • Mice
  • Mice, Inbred NOD
  • Mice, Nude
  • Mice, SCID
  • Mice, Transgenic
  • Neoplasm Transplantation
  • Pancreatic Neoplasms (blood supply, metabolism, pathology)
  • Transplantation, Heterologous
  • Tumor Microenvironment

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