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

被引：6

作者：

Abe, Toshiya ^{[1
]}

Ohuchida, Kenoki ^{[1
]}

Koikawa, Kazuhiro ^{[1
]}

Endo, Sho ^{[1
]}

Okumura, Takashi ^{[1
]}

Sada, Masafumi ^{[1
]}

Horioka, Kohei ^{[1
]}

Zheng, Biao ^{[1
]}

Moriyama, Taiki ^{[1
]}

Nakata, Kohei ^{[1
]}

Miyasaka, Yoshihiro ^{[1
]}

Manabe, Tatsuya ^{[1
]}

Ohtsuka, Takao ^{[1
]}

Nagai, Eishi ^{[1
]}

Mizumoto, Kazuhiro ^{[1
]}

Hashizume, Makoto ^{[2
]}

Nakamura, Masafumi ^{[1
]}

机构：

[1] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Oncol, 3-1-1 Maidashi, Fukuoka 8128582, Japan

[2] Kyushu Univ, Grad Sch Med Sci, Dept Adv Med Initiat, Fukuoka 8128582, Japan

来源：

INTERNATIONAL JOURNAL OF ONCOLOGY | 2017年 / 50卷 / 02期

基金：

日本学术振兴会;

关键词：

peritoneal mesothelial cells; pancreatic cancer; peritoneal dissemination; tumor-stromal interaction; remodeling; TO-MESENCHYMAL TRANSITION; STELLATE CELLS; CARCINOMATOSIS; FIBROBLASTS; ADHESION; MYOFIBROBLASTS; PROGRESSION; METASTASIS; MECHANISMS; PROMOTES;

D O I：

10.3892/ijo.2016.3829

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-Kras(G12D/+); LSL-Trp53(R172H/+);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.

引用

页码：457 / 467

页数：11

共 36 条

[1] Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer [J].