title: Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer.
abstract: Myofibroblasts in the stroma of pancreatic cancers promote tumor proliferation, invasion and metastasis by increasing extracellular matrix and secretion of several growth factors. In contrast, the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer has not yet been determined. This study was designed to assess the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer. Three primary cultures of human peritoneal myofibroblasts (hPMFs) were established from disseminated sites of pancreatic cancer and their interactions with the SUIT-2 and CAPAN-1 human pancreatic cancer cell lines were analyzed in vitro. Using a model in BALB/c nu/nu mice, we compared the dissemination ability of intraperitoneally implanted pancreatic cancer cells, with and without hPMFs, and examined the presence of green fluorescent protein (GFP)-labeled hPMFs at peritoneally disseminated sites in mice. hPMFs significantly promoted the migration and invasion of pancreatic cancer cells (P<0.05), while the cancer cells significantly promoted the migration and invasion of hPMFs (P<0.05). In vivo, the number of peritoneally disseminated nodules, more than 3 mm in size, was significantly greater in mice implanted with cancer cells plus hPMFs compared to mice implanted with cancer cells alone, with GFP-labeled hPMFs surviving in the peritoneal cavity of the former. hPMFs promote the peritoneal dissemination of pancreatic cancer. The cancer-stromal cell interaction in the peritoneal cavity may be a new therapeutic target to prevent the dissemination of pancreatic cancer.
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Akagawa
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Torata
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Hattori
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Eguchi
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kozono
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Lin
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ikenaga
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Ohtsuka
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Aishima
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D058628:Myofibroblasts / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009374:Neoplasms, Experimental; D010190:Pancreatic Neoplasms / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000556:secondary*; D010537:Peritoneum / Q000166:cytology* / Q000473:pathology