title: Orthotopic Implantation of Intact Tumor Tissue Leads to Metastasis of OCUM-2MD3 Human Gastric Cancer in Nude Mice Visualized in Real Time by Intravital Fluorescence Imaging.
abstract: OBJECTIVE
  Orthotopic (literally "correct place") implantation of cancer in nude mice has long been known to be superior to subcutaneous transplantation because the orthotopic tumor can metastasize. We reported previously on surgical orthotopic implantation (SOI) of gastric cancer tissue in nude mice resulting in the formation of metastases in 100% of the mice with extensive primary growth to the regional lymph nodes, liver, and lung. In contrast, when cell suspensions were used to inject gastric cancer cells orthotopically, metastases occurred in only 6.7% of the mice with local tumor formation, emphasizing the importance of orthotopically implanting intact tissue to allow full expression of metastatic potential. However, the different behavior of tumors implanted orthotopically by the two methods has not been visualized in real time.
  
  
  METHODS
  OCUM-2MD3 human gastric cancer cells labeled with the fluorescent protein Azami-Green were implanted orthotopically as cells or tissue in nude mice.
  
  
  RESULTS
  Orthotopic implantation of cells resulted in local spread on the stomach. In contrast, SOI of tumor tissue of OCUM-2MD3 resulted in vessel spread of the Azami-Green-expressing cancer cells. Metastasis was also observed in the left lobe of the liver after SOI.
  
  
  CONCLUSIONS
  These results demonstrate the physiological importance of intact cancer tissue for orthotopic implantation in order for tumors to properly grow and express their metastatic potential.
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A. Department of Surgery, University of California San Diego, San Diego, CA, U.S.A. Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Murakami
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A.
authors.forename: Xiaoen
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kasashima
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yashiro
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
authors.affiliation: Open Innovation Department, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miwa
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Kiyuna
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Ryusei
authors.initials: R
authors.lastname: Matsuyama
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Kuniya
authors.initials: K
authors.lastname: Tanaka
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: AntiCancer, Inc., San Diego, CA, U.S.A.
authors.forename: Itaru
authors.initials: I
authors.lastname: Endo
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.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D061848:Optical Imaging; D013274:Stomach Neoplasms / Q000473:pathology*
keywords: Azami-Green; Stomach cancer; cells; imaging; intravital; metastasis; orthotopic; tissue