Establishment of a novel model of peritoneal carcinomatosis of the peritoneal extension type.

AIM Patients with scirrhous carcinoma of the gastrointestinal tract frequently develop peritoneal carcinomatosis-particularly of the peritoneal extension type (PET), which has a bad prognosis. We developed a novel animal model, suitable for testing treatments for PET. MATERIAL AND METHODS In order to develop the model, we scraped the entire peritoneum of Fischer 344 rats with sterile cotton swabs and injected 1 × 10(6) cells of the RCN-9 cell type into the peritoneal cavity. RESULTS In the novel experimental model, RCN-9 cells adhered only to the exposed basement membrane. The submesothelial layer and fibroblasts in the submesothelial layer grew and increased to a maximum at day 7, then decreased during late-phase peritoneal carcinomatosis. At day 14, RCN-9 cells coated the peritoneum in a manner similar to PET. CONCLUSION We successfully established a novel animal model of peritoneal carcinomatosis that mimics clinicopathological features of PET. Fibroblasts in the submesothelial layer potentially play an important role in peritoneal carcinomatosis.

[1]  Y. Kodera,et al.  Gastric cancer treatment in Japan: 2008 annual report of the JGCA nationwide registry , 2011, Gastric Cancer.

[2]  M. Wei,et al.  Micro‐RNA‐21 regulates TGF‐β‐induced myofibroblast differentiation by targeting PDCD4 in tumor‐stroma interaction , 2011, International journal of cancer.

[3]  R. Bleichrodt,et al.  Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery for peritoneal carcinomatosis in an experimental model , 2010, The British journal of surgery.

[4]  H. Shiozaki,et al.  Increased Osteopontin-Positive Macrophage Expression in Colorectal Cancer Stroma with Synchronous Liver Metastasis , 2010, World Journal of Surgery.

[5]  M. Wei,et al.  CLIC4 mediates TGF-beta1-induced fibroblast-to-myofibroblast transdifferentiation in ovarian cancer. , 2009, Oncology reports.

[6]  Y. Yonemura,et al.  Current status and future strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis. , 2008, World journal of gastroenterology.

[7]  E. Sahai,et al.  Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells , 2007, Nature Cell Biology.

[8]  Yan Li,et al.  Intraperitoneal chemotherapy with hydroxycamptothecin reduces peritoneal carcinomatosis: results of an experimental study , 2007, Journal of Cancer Research and Clinical Oncology.

[9]  A. Oshima,et al.  Reciprocal Modifications of CLIC4 in Tumor Epithelium and Stroma Mark Malignant Progression of Multiple Human Cancers , 2007, Clinical Cancer Research.

[10]  Raghu Kalluri,et al.  Fibroblasts in cancer , 2006, Nature Reviews Cancer.

[11]  D. Jayne,et al.  Tumour-induced apoptosis in human mesothelial cells: a mechanism of peritoneal invasion by Fas Ligand/Fas interaction , 2004, British Journal of Cancer.

[12]  V. Antony,et al.  Defensive role of pleural mesothelial cell sialomucins in tumor metastasis. , 2003, Chest.

[13]  Meng Yang,et al.  Real-time optical imaging of primary tumor growth and multiple metastatic events in a pancreatic cancer orthotopic model. , 2002, Cancer research.

[14]  U. Heemann,et al.  Kupffer cells of cirrhotic rat livers sensitize colon cancer cells to Fas-mediated apoptosis , 2001, British Journal of Cancer.

[15]  J. Faure,et al.  Peritoneal carcinomatosis from non‐gynecologic malignancies , 2000, Cancer.

[16]  K. Hatakeyama,et al.  Blood Flow and Leukocyte Adhesiveness Are Reduced in the Microcirculation of a Peritoneal Disseminated Colon Carcinoma , 1998, Annals of Biomedical Engineering.

[17]  T. Yasuda,et al.  Extended surgery—Left upper abdominal exenteration plus Appleby's method—For type 4 gastric carcinoma , 1997, Annals of Surgical Oncology.

[18]  Y. Chung,et al.  Hepatocyte growth factor (HGF) produced by peritoneal fibroblasts may affect mesothelial cell morphology and promote peritoneal dissemination , 1996, International journal of cancer.

[19]  M. Yashiro,et al.  Fibrosis in the peritoneum induced by Scirrhous gastric cancer cells may act as “soil” for peritoneal dissemination , 1996, Cancer.

[20]  K. Aizawa,et al.  A New Rat Colon Cancer Cell Line Metastasizes Spontaneously: Biologic Characteristics and Chemotherapeutic Response , 1991, Japanese journal of cancer research : Gann.

[21]  Phillip Ruiz,et al.  Primary linitis plastica carcinoma of the colon and rectum. , 1989, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[22]  岩佐 悟 First-line fluorouracil-based chemotherapy for patients with severe peritoneal disseminated gastric cancer , 2013 .

[23]  Ken Kato,et al.  First-line fluorouracil-based chemotherapy for patients with severe peritoneal disseminated gastric cancer , 2011, Gastric Cancer.

[24]  M. Bracke Role of adhesion molecules in locoregional cancer spread. , 2007, Cancer treatment and research.

[25]  N. Ohshima,et al.  Angiogenic vascular growth in the rat peritoneal disseminated tumor model. , 1996, Microvascular research.