title: Development of a metastatic murine colon cancer model.
abstract: BACKGROUND
  It has now become clear that the complex interplay of cancer and the immune responses against it plays a critical role in the tumor microenvironment during cancer progression. As new targets for cancer treatment are being discovered and investigated, murine models used for preclinical studies need to include intact immune responses to provide a closer correlation with human cancer. We have recently developed a modified syngeneic orthotopic murine colon cancer model that mimics human colon cancer progression with consistent results.
  
  
  METHODS
  Tumors were created using the murine colon adenocarcinoma cell line, CT26, modified to overexpress the firefly luciferase gene (CT26-luc1), which allowed real-time in vivo monitoring of tumor burden when the substrate, D-luciferin, was injected intraperitoneally using the In Vivo Imaging System. Mice are Balb/c (Harlan), syngeneic with the CT26-luc1 cells. Cells are injected submucosally, suspended in Matrigel, into the cecum wall under direct visualization.
  
  
  RESULTS
  The model has demonstrated consistent implantation in the cecum. In vivo bioluminescence allowed real-time monitoring of total tumor burden. Perioperative preparation had a significant impact on reproducibility of the model. Finally, total tumor burden quantified with bioluminescence enabled estimation of lymph node metastasis ex vivo.
  
  
  CONCLUSIONS
  This method maintains an intact immune response and closely approximates the clinical tumor microenvironment. It is expected to provide an invaluable murine metastatic colon cancer model particularly in preclinical studies for drug development targeting those mechanisms.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and Massey Cancer Center, Richmond, Virginia.
authors.forename: Krista P
authors.initials: KP
authors.lastname: Terracina
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and Massey Cancer Center, Richmond, Virginia; Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Aoyagi
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and Massey Cancer Center, Richmond, Virginia; Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Wei-Ching
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and Massey Cancer Center, Richmond, Virginia; Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nagahashi
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and Massey Cancer Center, Richmond, Virginia; Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Division of Gene and Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Aoki
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and Massey Cancer Center, Richmond, Virginia; Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia. Electronic address: ktakabe@vcu.edu.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Takabe
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000473:pathology*; D047368:Tumor Burden
keywords: Animal model; Bioluminescence; Colon cancer; Metastasis; Orthotopic; Syngeneic