title: Establishing a xenograft mouse model of peritoneal dissemination of gastric cancer with organ invasion and fibrosis.
abstract: The clinical prognosis of gastric cancer with peritoneal dissemination is poor because of its chemoresistance and rich fibrosis. While several gastric cancer cell lines have been used to establish models of peritoneal dissemination by intraperitoneal injection, most peritoneal tumors that form adopt a medullary pattern in microscopic appearance. This histological finding for the model differs from that in the clinical situation. This study was performed to demonstrate the contribution of human peritoneal mesothelial cells (HPMCs) to fibrotic tumor formation and to establish a new xenograft model with high potential for peritoneal dissemination with organ invasion and extensive fibrosis.
  
  
  
  We established four types of xenograft model: i) intraperitoneal injection of MKN45-P cells alone (control group), ii) injection of MKN45-P cells co-cultured with HPMCs (co-cultured group), iii) scratching the parietal peritoneum (parietal group), and iv) scratching the visceral peritoneum (visceral group) with a cotton swab before injection of co-cultured cells. Fibrosis, α-smooth muscle actin expression, and organ invasion by tumor cells were all assessed by immunohistochemical examination.
  
  
  
  All mice developed abdominal swelling with peritoneal tumors and bloody ascites. Tumors of the control and co-cultured groups were not invasive or fibrotic. Contrastingly, tumors of the scratch groups exhibited rich stromal fibrosis and possessed increased α-smooth muscle actin (α-SMA) expression. In particular, the visceral group showed edematous and spreading tumors invading the intestinal wall.
  
  
  
  We established a model of peritoneal dissemination with organ invasion and stromal fibrosis. Formation of peritoneal dissemination required a favorable environment for cell adhesion, invasion, and growth. This model may be useful for analyzing the pathogenesis and treatment of peritoneal dissemination of gastric cancer.
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Ishikawa, Japan. mitsuyoshi0610@yahoo.co.jp.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Okazaki
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Ishikawa, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Fushida
authors.affiliation: Center for Biomedical Research and Education, School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Ishikawa, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Harada
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Ishikawa, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Tsukada
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Ishikawa, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kinoshita
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Ishikawa, Japan.
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Oyama
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Ishikawa, Japan.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Miyashita
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Ishikawa, Japan.
authors.forename: Itasu
authors.initials: I
authors.lastname: Ninomiya
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Ishikawa, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000473:pathology; D064593:Heterografts; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010534:Peritoneal Neoplasms / Q000556:secondary*; D010537:Peritoneum / Q000473:pathology; D013274:Stomach Neoplasms / Q000473:pathology*
keywords: Fibrosis; Gastric cancer; Organ invasion; Peritoneal dissemination