Human breast cancer-associated fibroblasts enhance cancer cell proliferation through increased TGF-α cleavage by ADAM17

被引：57

作者：

Gao, Ming-Qing ^{[1
,4
]}

Kim, Baek Gil ^{[1
]}

Kang, Suki ^{[1
,3
]}

Choi, Yoon Pyo ^{[2
]}

Yoon, Joo-Heon ^{[3
]}

Cho, Nam Hoon ^{[1
,2
,3
]}

机构：

[1] Yonsei Univ, Coll Med, Dept Pathol, Seoul 120752, South Korea

[2] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul 120752, South Korea

[3] Severance Biomed Sci Inst, Seoul 120752, South Korea

[4] Northwest A&F Univ, Coll Vet Med, Yangling 712100, Shaanxi, Peoples R China

来源：

CANCER LETTERS | 2013年 / 336卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

ADAM17; Breast cancer; Cancer-associated fibroblasts; TGF-alpha; Cell proliferation; STROMAL FIBROBLASTS; TACE INHIBITORS; METALLOPROTEINASES; PROGRESSION; ACTIVATION; GROWTH; EGFR; EXPRESSION; INTERFACE; RECEPTOR;

D O I：

10.1016/j.canlet.2013.05.011

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

We demonstrate here increased expression of ADAM17 protein in cancer-associated fibroblasts (CAFs) extracted from human breast carcinomas compared with donor-matched normal fibroblasts, and TGF-alpha secretion positively correlates with ADAM17 expression in these cells. In SK-BR-3 cells co-cultured with CAFs, CAF-secreted TGF-alpha promotes cell proliferation by activation of EGFR, Akt, and ERIC, but it does not promote cell migration. Furthermore, anti-TGF-alpha neutralizing antibodies antagonize the CAF-dependent increase in proliferation and activation of EGFR, Akt and ERIC. Thus, pharmacologic inhibition of ADAM17 and TGF-alpha may have therapeutic potential for the treatment of breast cancer when fibroblast-directed therapy is considered. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

引用

页码：240 / 246

页数：7

共 27 条

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