Adipocyte-Derived Fibroblasts Promote Tumor Progression and Contribute to the Desmoplastic Reaction in Breast Cancer

被引：422

作者：

Bochet, Ludivine ^{[1
,2
,3
,4
]}

Lehuede, Camille ^{[1
,2
,3
,4
]}

Dauvillier, Stephanie ^{[1
,2
,3
]}

Wang, Yuan Yuan ^{[1
,2
,3
,4
]}

Dirat, Beatrice ^{[1
,2
,3
,4
]}

Laurent, Victor ^{[1
,2
,3
]}

Dray, Cedric ^{[1
,4
]}

Guiet, Romain ^{[1
,2
,3
]}

Maridonneau-Parini, Isabelle ^{[1
,2
,3
]}

Le Gonidec, Sophie ^{[1
,4
]}

Couderc, Bettina ^{[5
]}

Escourrou, Ghislaine ^{[6
]}

Valet, Philippe ^{[1
,4
]}

Muller, Catherine ^{[1
,2
,3
]}

机构：

[1] Univ Toulouse, UPS, Toulouse, France

[2] CNRS, Toulouse, France

[3] Inst Pharmacol & Biol Struct, F-31077 Toulouse, France

[4] Fac Med Toulouse, INSERM, U1048, F-31073 Toulouse, France

[5] Inst Claudius Regaud, EA3035, Toulouse, France

[6] Hop Rangueil, Serv Anatomopathol, Toulouse, France

来源：

CANCER RESEARCH | 2013年 / 73卷 / 18期

关键词：

ADIPOSE-TISSUE; BETA-CATENIN; CELL-LINES; DIFFERENTIATION; ADIPOGENESIS; INVASION; MICROENVIRONMENT; EXPRESSION; SECRETION; EXHIBIT;

D O I：

10.1158/0008-5472.CAN-13-0530

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Cancer-associated fibroblasts (CAF) comprise the majority of stromal cells in breast cancers, yet their precise origins and relative functional contributions to malignant progression remain uncertain. Local invasion leads to the proximity of cancer cells and adipocytes, which respond by phenotypical changes to generate fibroblast-like cells termed as adipocyte-derived fibroblasts (ADF) here. These cells exhibit enhanced secretion of fibronectin and collagen I, increased migratory/invasive abilities, and increased expression of the CAF marker FSP-1 but not alpha-SMA. Generation of the ADF phenotype depends on reactivation of the Wnt/beta-catenin pathway in response to Wnt3a secreted by tumor cells. Tumor cells cocultivated with ADFs in two-dimensional or spheroid culture display increased invasive capabilities. In clinical specimens of breast cancer, we confirmed the presence of this new stromal subpopulation. By defining a new stromal cell population, our results offer new opportunities for stroma-targeted therapies in breast cancer. (C) 2013 AACR.

引用

页码：5657 / 5668

页数：12

共 34 条

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