Mesenchymal stem cells regulate epithelial-mesenchymal transition and tumor progression of pancreatic cancer cells

被引：122

作者：

Kabashima-Niibe, Ayano ^{[1
]}

Higuchi, Hajime ^{[1
]}

Takaishi, Hiromasa ^{[1
]}

Masugi, Yohei ^{[2
]}

Matsuzaki, Yumi ^{[3
]}

Mabuchi, Yo ^{[3
]}

Funakoshi, Shinsuke ^{[1
]}

Adachi, Masayuki ^{[1
]}

Hamamoto, Yasuo ^{[1
]}

Kawachi, Shigeyuki ^{[4
]}

Aiura, Koichi ^{[5
]}

Kitagawa, Yuko ^{[6
]}

Sakamoto, Michiie ^{[2
]}

Hibi, Toshifumi ^{[1
]}

机构：

[1] Keio Univ, Sch Med, Dept Internal Med, Div Gastroenterol, Tokyo, Japan

[2] Keio Univ, Sch Med, Dept Pathol, Tokyo 160, Japan

[3] Keio Univ, Sch Med, Dept Physiol, Tokyo 160, Japan

[4] Tokyo Med Univ, Hachioji Med Ctr, Dept Digest Surg & Transplantat Surg, Tokyo 1608402, Japan

[5] Kawasaki Municipal Hosp, Dept Surg, Kawasaki, Kanagawa, Japan

[6] Keio Univ, Sch Med, Dept Surg, Tokyo 160, Japan

来源：

CANCER SCIENCE | 2013年 / 104卷 / 02期

关键词：

MARROW-DERIVED CELLS; RBP-J-KAPPA; SIDE POPULATION; DOWN-REGULATION; GROWTH-FACTOR; NOTCH; FIBROBLASTS; APOPTOSIS; DIFFERENTIATION; MYOFIBROBLASTS;

D O I：

10.1111/cas.12059

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cancer-associated fibroblasts contribute to cancer progression that is caused by epithelialmesenchymal transition (EMT). Recently, mesenchymal stem cells (MSCs) were found to be the major candidate involved in the development of tumor-promoting cancer stroma. Here we report that -smooth muscle actin-positive myofibroblast-like cells originating from MSCs contribute to inducing EMT in side population cells of pancreatic cancer. More importantly, MSC-derived myofibroblasts function to maintain tumor-initiating stem cell-like characteristics, including augmenting expression levels of various stemness-associated genes, enhancing sphere- forming activity, promoting tumor formation in a mouse xenograft model, and showing resistance to anticancer drugs. Furthermore, both -secretase inhibitor and siRNA directed against Jagged-1 attenuated MSC-associated E-cadherin suppression and sphere formation in pancreatic cancer side population cells. Thus, our results suggest that MSC-derived myofibroblasts play important roles in regulating EMT and tumor-initiating stem cell-like properties of pancreatic cancer cells through an intermediating Notch signal.

引用

页码：157 / 164

页数：8

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