Disequilibrium of BMP2 Levels in the Breast Stem Cell Niche Launches Epithelial Transformation by Overamplifying BMPRIB Cell Response

被引：47

作者：

Chapellier, Marion ^{[1
,2
,3
,4
,5
]}

Bachelard-Cascales, Elodie ^{[6
]}

Schmidt, Xenia ^{[1
,2
,3
,4
,5
]}

Clement, Flora ^{[1
,2
,3
,4
,5
]}

Treilleux, Isabelle ^{[1
,2
,3
,4
,5
,7
]}

Delay, Emmanuel ^{[1
,2
,3
,4
,5
,7
]}

Jammot, Alexandre ^{[1
,2
,3
,4
,5
]}

Menetrier-Caux, Christine ^{[1
,2
,3
,4
,5
,7
]}

Pochon, Gaetan ^{[1
,2
,3
,4
,5
]}

Besancon, Roger ^{[1
,2
,3
,4
,5
]}

Voeltzel, Thibault ^{[1
,2
,3
,4
,5
]}

de Fromentel, Claude Caron ^{[1
,2
,3
,4
,5
]}

Caux, Christophe ^{[1
,2
,3
,4
,5
,7
]}

Blay, Jean-Yves ^{[1
,2
,3
,4
,5
,7
]}

Iggo, Richard ^{[6
]}

Maguer-Satta, Veronique ^{[1
,2
,3
,4
,5
]}

机构：

[1] CNRS, UMR5286, Ctr Rech Cancerol Lyon, F-69000 Lyon, France

[2] Ctr Rech Cancerol Lyon, Inserm U1052, F-69000 Lyon, France

[3] Univ Lyon, F-69000 Lyon, France

[4] Dept Immun Virus & Microenvironm, F-69000 Lyon, France

[5] Univ Lyon 1, ISPB, F-69000 Lyon, France

[6] Univ Bordeaux, Inst Bergonie, INSERM, F-33076 Bordeaux, France

[7] Ctr Leon Berard, F-69000 Lyon, France

来源：

STEM CELL REPORTS | 2015年 / 4卷 / 02期

关键词：

BONE MORPHOGENETIC PROTEIN-2; HUMAN MAMMARY-GLAND; CANCER-CELLS; IN-VIVO; PROGENITORS; DIFFERENTIATION; IDENTIFICATION; INFLAMMATION; METASTASIS; EXPRESSION;

D O I：

10.1016/j.stemcr.2014.12.007

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Understanding the mechanisms of cancer initiation will help to prevent and manage the disease. At present, the role of the breast micro-environment in transformation remains unknown. As BMP2 and BMP4 are important regulators of stem cells and their niches in many tissues, we investigated their function in early phases of breast cancer. BMP2 production by tumor microenvironment appeared to be specifically upregulated in luminal tumors. Chronic exposure of immature human mammary epithelial cells to high BMP2 levels initiated transformation toward a luminal tumor-like phenotype, mediated by the receptor BMPR1B. Under physiological conditions, BMP2 controlled the maintenance and differentiation of early luminal progenitors, while BMP4 acted on stem cells/myoepithelial progenitors. Our data also suggest that microenvironment-induced overexpression of BMP2 may result from carcinogenic exposure. We reveal a role for BMP2 and the breast microenvironment in the initiation of stem cell transformation, thus providing insight into the etiology of luminal breast cancer.

引用

页码：239 / 254

页数：16

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