title: Imaging Nuclear-Cytoplasmic Dynamics in Primary and Metastatic Colon Cancer in Nude Mice.
abstract: BACKGROUND
  Colon cancer frequently results in metastasis to the liver, where it becomes the main cause of death. However, the cell cycle in primary tumors and metastases is poorly understood.
  
  
  METHODS
  We developed a mouse model of liver metastasis using the human colon cancer cell line HCT-116, which expresses green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm (HCT-116-GFP-RFP). HCT-116 GFP-RFP cells were injected into the spleen of nu/nu nude mice.
  
  
  RESULTS
  HCT-116-GFP-RFP cells subsequently formed primary tumors in the spleen, as well as metastatic colonies in the liver and retroperitoneum by 28 days after cell transplantation. Using an Olympus FV1000 confocal microscope, it was possible to clearly image mitosis of the dual-colored colon cancer cells in the primary tumor as well as liver and other metastases. Multi-nucleate cancer cells, in addition to mono-nucleate cancer cells and their mitosis, were observed in the primary tumor and metastasis. Multi-nucleate HCT-116-GFP-RFP cells were also observed after culture of the primary and metastatic tumors. A similar ratio of mono-nucleate, multi-nucleate, and mitotic cells grew from the primary and metastatic tumors in culture, suggesting similarity of the nuclear-cytoplasmic dynamics of primary and metastatic cancer cells, further emphasizing the stochastic nature of metastasis.
  
  
  CONCLUSIONS
  Our results demonstrate a similar heterogeneity of nuclear-cytoplasmic dynamics within primary tumors and metastases, which may be an important factor in the stochastic nature of metastasis.
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan AntiCancer, Inc., San Diego, CA, U.S.A. Department of Surgery, University of California San Diego, 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: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Aoki
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kunisada
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, CA, U.S.A.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.affiliation: Department of Gastroenterology, 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, 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: D000818:Animals; D002467:Cell Nucleus / Q000473:pathology*; D003110:Colonic Neoplasms / Q000473:pathology*; D003593:Cytoplasm / Q000473:pathology*; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis
keywords: Dual color cancer cells; GFP; RFP; colon cancer; imaging; liver metastasis; mitosis; nude mice