title: A Color-coded Imageable Syngeneic Mouse Model of Stromal-cell Recruitment by Metastatic Lymphoma.
abstract: OBJECTIVE
  A syngeneic color-coded imageable lymphoma model has been developed to visualize recruitment of host stromal cells by malignant lymphoma during metastasis. The EL4 cell line was previously derived from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene.
  
  
  METHODS
  EL4 lymphoma cells expressing red fluorescent protein (EL4-RFP) were initially established. EL4-RFP cells were subsequently injected into the tail vein of C57/BL6-GFP transgenic mice.
  
  
  RESULTS
  EL4-RFP metastasis was observed in the lymph nodes of the upper mediastinum and in the liver 28 days after cell injection. Large EL4-RFP liver metastases in C57/BL6-GFP mice contained GFP-expressing stromal cells derived from the host. In addition, EL4-RFP lymphoma metastasis was formed in peri-gastric lymph nodes, which were also enriched in host GFP-expressing cells. Furthermore, EL4-RFP lymphoma cells were also observed in the peripheral blood and bone marrow of C57/BL6-GFP transgenic mice, where they were associated with GFP-expressing host cells.
  
  
  CONCLUSIONS
  Lymph node, liver and bone marrow metastases were found approximately 4 weeks after transplantation and all RFP-expressing metastases were highly enriched in GFP-expressing host stromal cells. This model of malignant lymphoma can be used to study early tumor development, metastasis, and the role of the stroma, as well as for discovery and evaluation of novel therapeutics for this treatment-resistant disease.
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan AntiCancer Inc., San Diego, CA, U.S.A. Department of Surgery, University of California, San Diego, CA, U.S.A. all@anticancer.com asue@gifu-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suetsugu
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Aoki
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kunisada
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tsurumi
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: AntiCancer Inc., San Diego, CA, U.S.A. Department of Surgery, University of California, San Diego, CA, U.S.A. all@anticancer.com asue@gifu-u.ac.jp.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D045744:Cell Line, Tumor; D003116:Color; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D005453:Fluorescence; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008113:Liver Neoplasms / Q000556:secondary*; D008223:Lymphoma / Q000473:pathology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017154:Stromal Cells / Q000473:pathology
chemical_list: D049452:Green Fluorescent Proteins; D015127:9,10-Dimethyl-1,2-benzanthracene
keywords: C57/BL6-GFP mice; RFP; imaging; liver metastasis; malignant lymphoma