title: Color-coded imaging of splenocyte-pancreatic cancer cell interactions in the tumor microenvironment.
abstract: In spite of advances in surgical and medical care, pancreatic cancer remains a leading cause of cancer-related death in the United States. An understanding of cancer-cell interactions with host cells is critical to our ability to develop effective antitumor therapeutics for pancreatic cancer. We report here a color-coded model system for imaging cancer cell interactions with host immune cells within the native pancreas. A human pancreatic cancer cell line engineered to express green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) (DsRed2) in the cytoplasm was orthotopically implanted into the pancreas of a nude mouse. After 10-14 days, red or green fluorescent splenocytes from immune-competent transgenic-mouse donors expressing RFP and GFP, respectively, were delivered systemically to the pancreatic cancer-bearing nude mice. Animals were imaged after splenocyte delivery using high-resolution intravital imaging systems. At 1 day after iv injection red- or green-fluorescent spleen cells were found distributed in lung, liver, spleen and pancreas. By 4 days after cell delivery, however, the immune cells could be clearly imaged surrounding the tumor cells within the pancreas as well as collecting within lymphatic tissues such as lymph nodes and spleen. With the high-resolution intravital imaging afforded by the Olympus IV100 and OV100 systems, the interactions of the dual-colored cancer cells and the red- or green-fluorescent spleen cells could be clearly imaged in this orthotopic pancreatic cancer model. This color-coded in vivo imaging technology offers a novel approach to imaging the interactions of cancer and immune cells in the tumor microenvironment (TME).
authors.affiliation: Department of Surgery, University of California, San Diego, California, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: McElroy
authors.forename: Sharmeela
authors.initials: S
authors.lastname: Kaushal
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D002450:Cell Communication; D003116:Color; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000473:pathology*; D013154:Spleen / Q000166:cytology*
chemical_list: D049452:Green Fluorescent Proteins
references.citation: Cell Cycle. 2006 Aug;5(16):1886-901
references.pmid: 16963837
references.citation: Genes Dev. 1999 Jun 1;13(11):1382-97
references.pmid: 10364156
references.citation: Cancer Metastasis Rev. 2006 Dec;25(4):521-9
references.pmid: 17186383
references.citation: Cancer Metastasis Rev. 2008 Mar;27(1):11-8
references.pmid: 18066650
references.citation: Cancer Res. 2007 Dec 15;67(24):11687-95
references.pmid: 18089798
references.citation: Cancer Res. 2008 Apr 1;68(7):2085-93
references.pmid: 18381413
references.citation: Cell Cycle. 2006 Jan;5(2):191-7
references.pmid: 16357534
references.citation: Cancer Res. 2006 Jan 1;66(1):259-66
references.pmid: 16397239
references.citation: Nat Protoc. 2006;1(3):1429-38
references.pmid: 17406431
references.citation: Pancreas. 2004 Oct;29(3):179-87
references.pmid: 15367883
references.citation: Nat Cell Biol. 2006 Dec;8(12):1369-75
references.pmid: 17128264
references.citation: Nat Rev Cancer. 2005 Oct;5(10):796-806
references.pmid: 16195751
references.citation: Nat Cell Biol. 2000 Oct;2(10):737-44
references.pmid: 11025665
references.citation: Nature. 2004 Sep 23;431(7007):405-6
references.pmid: 15385993
references.citation: Br J Cancer. 2001 Nov 30;85(11):1655-63
references.pmid: 11742483
references.citation: Cancer Res. 2008 Feb 1;68(3):918-26
references.pmid: 18245495
references.citation: PLoS One. 2007 Oct 24;2(10):e1075
references.pmid: 17957257
references.citation: Q J Nucl Med Mol Imaging. 2005 Dec;49(4):361-6
references.pmid: 16407819
references.citation: Nat Rev Immunol. 2005 Oct;5(10):749-59
references.pmid: 16175180
references.citation: Cell. 2006 Jan 27;124(2):263-6
references.pmid: 16439202
references.citation: Gastroenterology. 2005 May;128(6):1626-41
references.pmid: 15887155
references.citation: Cell Cycle. 2007 Nov 1;6(21):2706-8
references.pmid: 17912040
references.citation: Cancer Res. 2007 Jun 1;67(11):5195-200
references.pmid: 17545599
references.citation: Nat Protoc. 2006;1(2):928-35
references.pmid: 17406326
references.citation: Genesis. 2004 Dec;40(4):241-6
references.pmid: 15593332
references.citation: Cell Cycle. 2006 Jun;5(11):1198-201
references.pmid: 16760659
references.citation: Gastroenterology. 2005 Apr;128(4):907-21
references.pmid: 15825074
references.citation: Surgery. 2007 May;141(5):610-8
references.pmid: 17462460
references.citation: Pancreas. 1995 Nov;11(4):345-9
references.pmid: 8532650
references.citation: Nat Protoc. 2006;1(2):775-82
references.pmid: 17406307
references.citation: Nat Med. 2006 Mar;12(3):354-60
references.pmid: 16501571
references.citation: Nature. 2002 Dec 19-26;420(6917):860-7
references.pmid: 12490959
references.citation: Cancer Cell. 2005 Mar;7(3):211-7
references.pmid: 15766659