Nab-paclitaxel interrupts cancer-stromal interaction through C-X-C motif chemokine 10-mediated interleukin-6 downregulation in vitro

被引：40

作者：

Feng, Rui ^{[1
]}

Morine, Yuji ^{[1
]}

Ikemoto, Tetsuya ^{[1
]}

Imura, Satoru ^{[1
]}

Iwahashi, Shuichi ^{[1
]}

Saito, Yu ^{[1
]}

Shimada, Mitsuo ^{[1
]}

机构：

[1] Univ Tokushima, Grad Sch, Inst Biomed Sci, Dept Surg, Tokushima, Japan

来源：

CANCER SCIENCE | 2018年 / 109卷 / 08期

关键词：

130 nm albumin-bound paclitaxel; cancer-associated fibroblast; chemokine CXCL10; epithelial-mesenchymal transition; pancreatic neoplasms; INCREASED ANTITUMOR-ACTIVITY; PANCREATIC STELLATE CELLS; CARCINOMA CELLS; FIBROBLASTS; PROGRESSION; ACTIVATION; FIBROSIS; CXCL10;

D O I：

10.1111/cas.13694

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cancer-associated fibroblasts (CAF), derived from stroma of cancer tissues, interact with cancer cells and play an important role in cancer initiation, growth, and metastasis. Nab-paclitaxel (nab-PTX) is a 130 nm albumin-binding paclitaxel and recommended for many types of cancer chemotherapy. The nab-PTX stromal-disrupting effect during pancreatic cancer treatment has been reported. The aim of the present study was to determine the role of nab-PTX in cancer cells and CAF interaction. Cancer cells (MIA PaCa-2 and Panc-1) were cocultured with CAF or treated with CAF conditioned medium, after which their migration and invasion ability, epithelial-mesenchymal transition (EMT)-related marker expression and C-X-C motif chemokine 10 (CXCL10) expression and secretion were detected. Nab-PTX treatment was carried out during the coculture system or during preparation of CAF conditioned medium. Then cancer cell migration and invasion ability, EMT-related marker expression, CXCL10 expression and secretion, and interleukin-6 (IL-6) expression and secretion by CAF were checked After coculture with CAF, migration and invasion ability of cancer cells increased. CAF also downregulated E-cadherin and upregulated N-cadherin and vimentin expression in cancer cells. During coculture or stimulation with cancer cell-cultured medium, CAF significantly increased IL-6 expression and secretion. However, nab-PTX in the coculture system canceled CAF-induced migration and invasion promotion and EMT-related gene changes. Moreover, nab-PTX increased CXCL10 expression of cancer cells which blocked CAF IL-6 expression and secretion. Nab-PTX treatment could increase CXCL10 expression of cancer cells which blocks CAF cancer cell migration and invasion-promoting effect by inhibiting IL-6 expression.

引用

页码：2509 / 2519

页数：11

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