Cancer-associated peritoneal mesothelial cells lead the formation of pancreatic cancer peritoneal dissemination

Toshiya Abe, Kenoki Ohuchida, Kazuhiro Koikawa, Sho Endo, Takashi Okumura, Masafumi Sada, Kohei Horioka, Biao Zheng, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Tatsuya Manabe, Takao Ohtsuka, Eishi Nagai, Kazuhiro Mizumoto, Makoto Hashizume, Masafumi Nakamura

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Abstract

The interaction between the cancer cells and the peritoneal mesothelial cells (PMCs) plays an important role in the peritoneal dissemination in several types of cancer. However, the role of PMCs in the peritoneal dissemination of pancreatic cancer remains unclear. In the present study, we investigated the interaction between the pancreatic cancer cells (PCCs) and the PMCs in the formation of peritoneal dissemination in vitro and in vivo. The tumor-stromal interaction of PCCs and PMCs significantly enhanced their mobility and invasiveness and enhanced the proliferation and anoikis resistance of PCCs. In a 3D organotypic culture model of peritoneal dissemination, co-culture of PCCs and PMCs significantly increased the cells invading into the collagen gel layer compared with mono-culture of PCCs. PMCs pre-invaded into the collagen gel, remodeled collagen fibers, and increased parallel fiber orientation along the direction of cell invasion. In the tissues of peritoneal dissemination of the KPC (LSL-KrasG12D/+; LSL-Trp53R172H/+;Pdx-1-Cre) transgenic mouse, the monolayer of PMCs was preserved in tumor-free areas, whereas PMCs around the invasive front of peritoneal dissemination proliferated and invaded into the muscle layer. In vivo, intraperitoneal injection of PCCs with PMCs significantly promoted peritoneal dissemination compared with PCCs alone. The present data suggest that the cancer-associated PMCs have important promoting roles in the peritoneal dissemination of PCCs. Therapy targeting cancer-associated PMCs may improve the prognosis of patients with pancreatic cancer.

Original languageEnglish
Pages (from-to)457-467
Number of pages11
JournalInternational journal of oncology
Volume50
Issue number2
DOIs
Publication statusPublished - Feb 2017

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Pancreatic Neoplasms
Neoplasms
Collagen
Gels
Anoikis
Second Primary Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Cancer-associated peritoneal mesothelial cells lead the formation of pancreatic cancer peritoneal dissemination. / Abe, Toshiya; Ohuchida, Kenoki; Koikawa, Kazuhiro; Endo, Sho; Okumura, Takashi; Sada, Masafumi; Horioka, Kohei; Zheng, Biao; Moriyama, Taiki; Nakata, Kohei; Miyasaka, Yoshihiro; Manabe, Tatsuya; Ohtsuka, Takao; Nagai, Eishi; Mizumoto, Kazuhiro; Hashizume, Makoto; Nakamura, Masafumi.

In: International journal of oncology, Vol. 50, No. 2, 02.2017, p. 457-467.

Research output: Contribution to journalArticle

Abe, Toshiya ; Ohuchida, Kenoki ; Koikawa, Kazuhiro ; Endo, Sho ; Okumura, Takashi ; Sada, Masafumi ; Horioka, Kohei ; Zheng, Biao ; Moriyama, Taiki ; Nakata, Kohei ; Miyasaka, Yoshihiro ; Manabe, Tatsuya ; Ohtsuka, Takao ; Nagai, Eishi ; Mizumoto, Kazuhiro ; Hashizume, Makoto ; Nakamura, Masafumi. / Cancer-associated peritoneal mesothelial cells lead the formation of pancreatic cancer peritoneal dissemination. In: International journal of oncology. 2017 ; Vol. 50, No. 2. pp. 457-467.
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AU - Abe, Toshiya

AU - Ohuchida, Kenoki

AU - Koikawa, Kazuhiro

AU - Endo, Sho

AU - Okumura, Takashi

AU - Sada, Masafumi

AU - Horioka, Kohei

AU - Zheng, Biao

AU - Moriyama, Taiki

AU - Nakata, Kohei

AU - Miyasaka, Yoshihiro

AU - Manabe, Tatsuya

AU - Ohtsuka, Takao

AU - Nagai, Eishi

AU - Mizumoto, Kazuhiro

AU - Hashizume, Makoto

AU - Nakamura, Masafumi

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N2 - The interaction between the cancer cells and the peritoneal mesothelial cells (PMCs) plays an important role in the peritoneal dissemination in several types of cancer. However, the role of PMCs in the peritoneal dissemination of pancreatic cancer remains unclear. In the present study, we investigated the interaction between the pancreatic cancer cells (PCCs) and the PMCs in the formation of peritoneal dissemination in vitro and in vivo. The tumor-stromal interaction of PCCs and PMCs significantly enhanced their mobility and invasiveness and enhanced the proliferation and anoikis resistance of PCCs. In a 3D organotypic culture model of peritoneal dissemination, co-culture of PCCs and PMCs significantly increased the cells invading into the collagen gel layer compared with mono-culture of PCCs. PMCs pre-invaded into the collagen gel, remodeled collagen fibers, and increased parallel fiber orientation along the direction of cell invasion. In the tissues of peritoneal dissemination of the KPC (LSL-KrasG12D/+; LSL-Trp53R172H/+;Pdx-1-Cre) transgenic mouse, the monolayer of PMCs was preserved in tumor-free areas, whereas PMCs around the invasive front of peritoneal dissemination proliferated and invaded into the muscle layer. In vivo, intraperitoneal injection of PCCs with PMCs significantly promoted peritoneal dissemination compared with PCCs alone. The present data suggest that the cancer-associated PMCs have important promoting roles in the peritoneal dissemination of PCCs. Therapy targeting cancer-associated PMCs may improve the prognosis of patients with pancreatic cancer.

AB - The interaction between the cancer cells and the peritoneal mesothelial cells (PMCs) plays an important role in the peritoneal dissemination in several types of cancer. However, the role of PMCs in the peritoneal dissemination of pancreatic cancer remains unclear. In the present study, we investigated the interaction between the pancreatic cancer cells (PCCs) and the PMCs in the formation of peritoneal dissemination in vitro and in vivo. The tumor-stromal interaction of PCCs and PMCs significantly enhanced their mobility and invasiveness and enhanced the proliferation and anoikis resistance of PCCs. In a 3D organotypic culture model of peritoneal dissemination, co-culture of PCCs and PMCs significantly increased the cells invading into the collagen gel layer compared with mono-culture of PCCs. PMCs pre-invaded into the collagen gel, remodeled collagen fibers, and increased parallel fiber orientation along the direction of cell invasion. In the tissues of peritoneal dissemination of the KPC (LSL-KrasG12D/+; LSL-Trp53R172H/+;Pdx-1-Cre) transgenic mouse, the monolayer of PMCs was preserved in tumor-free areas, whereas PMCs around the invasive front of peritoneal dissemination proliferated and invaded into the muscle layer. In vivo, intraperitoneal injection of PCCs with PMCs significantly promoted peritoneal dissemination compared with PCCs alone. The present data suggest that the cancer-associated PMCs have important promoting roles in the peritoneal dissemination of PCCs. Therapy targeting cancer-associated PMCs may improve the prognosis of patients with pancreatic cancer.

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