Adipose Stroma Induces Branching Morphogenesis of Engineered Epithelial Tubules

Pavlovich, Amira L.; Manivannan, Sriram; Nelson, Celeste M.

doi:10.1089/ten.tea.2009.0836

Cited by 25 publications

(23 citation statements)

References 55 publications

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“…Most of the studies used the nonmammary mouse preadipocyte cell line 3T3-L1, 23,[40][41][42][43] conditioned media from other adipocyte cell lines, or mammary adipose tissue. 44,45 To overcome these limitations, we added human PA and adipocytes to our 3D morphogenesis model.…”

Section: Discussionmentioning

confidence: 99%

Dual Regulation of Breast Tubulogenesis Using Extracellular Matrix Composition and Stromal Cells

Krause

Jondeau-Cabaton²,

Dhimolea³

et al. 2012

Tissue Engineering Part A

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Epithelial-mesenchymal interactions during embryogenesis are critical in defining the phenotype of tissues and organs. The initial elongation of the mammary bud represents a central morphological event requiring extensive epithelial-mesenchymal crosstalk. The precise mechanism orchestrating this outgrowth is still unknown and mostly animal models have been relied upon to explore this process. Highly tunable three-dimensional (3D) culture models are a complementary approach to address the question of phenotypic determination. Here, we used a 3D in vitro culture to study the roles of stromal cells and extracellular matrix components during mammary tubulogenesis. Fibroblasts, adipocytes, and type I collagen actively participated in this process, whereas reconstituted basement membrane inhibited tubulogenesis by affecting collagen organization. We conclude that biochemical and biomechanical signals mediate the interaction between cells and matrix components and are necessary to induce tubulogenesis in vitro.

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Section: Discussionmentioning

confidence: 99%

Dual Regulation of Breast Tubulogenesis Using Extracellular Matrix Composition and Stromal Cells

Krause

Jondeau-Cabaton²,

Dhimolea³

et al. 2012

Tissue Engineering Part A

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“…6,14 However, how adipocyte-related MMP-11 acts at the physiological level remains largely unknown. As stromal cells are potent mediators in the proper development and maintenance of mammary ductal morphogenesis, [15][16][17][18][19][20] we hypothetized that MMP-11 might participate in this biological process.…”

Section: Introductionmentioning

confidence: 99%

Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development

et al. 2013

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MMP-11 is a bad prognosis paracrine factor in invasive breast cancers. However, its mammary physiological function remains largely unknown. In the present study we have investigated MMP-11 function during postnatal mammary gland development and function using MMP-11-deficient (MMP-11 À / À ) mice. Histological and immunohistochemical analyses as well as whole-mount mammary gland staining show alteration of the mammary gland in the absence of MMP-11, where ductal tree, alveolar structures and milk production are reduced. Moreover, a series of transplantation experiments allowed us to demonstrate that MMP-11 exerts an essential local paracrine function that favors mammary gland branching and epithelial cell outgrowth and invasion through adjacent connective tissues. Indeed, MMP-11 À / À cleared fat pads are not permissive for wild-type epithelium development, whereas MMP-11 À / À epithelium transplants grow normally when implanted in wild-type cleared fat pads. In addition, using primary mammary epithelial organoids, we show in vitro that this MMP-11 pro-branching effect is not direct, suggesting that MMP-11 acts via production/release of stroma-associated soluble factor(s). Finally, the lack of MMP-11 leads to decreased periductal collagen content, suggesting that MMP-11 has a role in collagen homeostasis. Thus, local stromal MMP-11 might also regulate mammary epithelial cell behavior mechanically by promoting extracellular matrix stiffness. Collectively, the present data indicate that MMP-11 is a paracrine factor involved during postnatal mammary gland morphogenesis, and support the concept that the stroma strongly impact epithelial cell behavior. Interestingly, stromal MMP-11 has previously been reported to favor malignant epithelial cell survival and promote cancer aggressiveness. Thus, MMP-11 has a paracrine function during mammary gland development that might be harnessed to promote tumor progression, exposing a new link between development and malignancy.

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“…Contact with breast cancer cells enhanced the differentiation of pre-adipocytes into adipocytes, and completely modified their transcriptional programs by increasing the expression of genes involved in cell proliferation (cyclinD1, MAPK), angiogenesis (MMP9, VEGF) and hormonal signaling (ESR1, IL6). Moreover, another 3D model of differentiated T3T-L1 adipocytes with normal murine mammary epithelial cells demonstrated that adipocyte-rich stroma induces branching through paracrine signals, including hepatocyte growth factor secretion, and may serve as a good model for observations during pubertal development (Pavlovich, et al 2010). The addition of POPs could show potential alterations in branching morphogenesis or initiation of pre-cancerous lesions during puberty.…”

Section: Pops Obesity and Breast Cancermentioning

confidence: 99%

Persistent organic pollutants and obesity: are they potential mechanisms for breast cancer promotion?

Reaves¹,

Ginsburg²,

Bang³

et al. 2015

Endocrine-Related Cancer

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Dietary ingestion of persistent organic pollutants (POPs) correlates with developing obesity. Obesity alters metabolism, induces an inflammatory tissue microenvironment, and is also linked with diabetes and breast cancer risk/promotion of the disease. However, no direct evidence exists exploring the correlation among all three of these factors (POPs, obesity, and breast cancer). Herein, we present current correlative studies suggesting a causal link between POPs exposure through diet and their bioaccumulation in adipose that promotes the development of obesity and ultimately influences breast cancer development and/or progression. Furthermore, as endocrine disruptors, POPs can potentially interfere with hormonally responsive tissue functions causing dysregulation in hormone signaling and cell function. This review highlights the critical need for advanced in vitro and in vivo model systems to understand the complex relationship between obesity, POPs, breast cancer, and, more importantly, to delineate their multifaceted molecular, cellular, and biochemical mechanisms. Comprehensive in vitro and in vivo studies directly testing the observed correlations as well as detailing their molecular mechanisms are vital to cancer research and, ultimately, public health.

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Adipose Stroma Induces Branching Morphogenesis of Engineered Epithelial Tubules

Cited by 25 publications

References 55 publications

Dual Regulation of Breast Tubulogenesis Using Extracellular Matrix Composition and Stromal Cells

Dual Regulation of Breast Tubulogenesis Using Extracellular Matrix Composition and Stromal Cells

Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development

Persistent organic pollutants and obesity: are they potential mechanisms for breast cancer promotion?

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