Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer

Akagawa,Shin; Ohuchida,Kenoki; Torata,Nobuhiro; Hattori,Masami; Eguchi,Daiki; Fujiwara,Kenji; Kozono,Shingo; Cui,Lin; Ikenaga,Naoki; Ohtsuka,Takao; Aishima,Shinichi; Mizumoto,Kazuhiro; Oda,Yoshinao; Tanaka,Masao

doi:10.3892/ijo.2014.2391

Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer

Authors:
- Shin Akagawa
- Kenoki Ohuchida
- Nobuhiro Torata
- Masami Hattori
- Daiki Eguchi
- Kenji Fujiwara
- Shingo Kozono
- Lin Cui
- Naoki Ikenaga
- Takao Ohtsuka
- Shinichi Aishima
- Kazuhiro Mizumoto
- Yoshinao Oda
- Masao Tanaka
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Affiliations: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Published online on: April 16, 2014 https://doi.org/10.3892/ijo.2014.2391
Pages: 113-120

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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.

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