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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
Author(s) -
Suetsugu Atsushi,
Katz Matthew,
Fleming Jason,
Truty Mark,
Thomas Ryan,
Moriwaki Hisataka,
Bouvet Michael,
Saji Shigetoyo,
Hoffman Robert M.
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24099
Subject(s) - stroma , green fluorescent protein , pancreatic cancer , cancer research , genetically modified mouse , pathology , nod , tumor microenvironment , biology , transgene , cancer , medicine , immunohistochemistry , tumor cells , gene , biochemistry , genetics
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. J. Cell. Biochem. 113: 2290–2295, 2012. © 2012 Wiley Periodicals, Inc.