Extracellular matrix in mammary gland development and breast cancer progression

Hu, Gaofeng; Li, Linzhang; Xu, Wei

doi:10.1016/j.flm.2017.02.008

Cited by 33 publications

(54 citation statements)

References 43 publications

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“…). This result can be attributed to the fact that the higher matrix stiffness can induce clustering of integrins which further activates proliferative pathways in breast cancer cells leading to tumor progression . Other studies pertaining to different malignancies like glioma and hepatocellular carcinoma have also observed the same trend in proliferation with hydrogel stiffness .…”

Section: Resultsmentioning

confidence: 68%

The influence of matrix stiffness on the behavior of brain metastatic breast cancer cells in a biomimetic hyaluronic acid hydrogel platform

Narkhede

Crenshaw

Manning

et al. 2018

J Biomedical Materials Res

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Breast cancer brain metastasis marks the most advanced stage of breast cancer no longer considered curable with a median survival period of ∼4-16 months. Apart from the genetic susceptibility (subtype) of breast tumors, brain metastasis is also dictated by the biophysical/chemical interactions of tumor cells with native brain microenvironment, which remain obscure, primarily due to the lack of tunable biomimetic in vitro models. To address this need, we utilized a biomimetic hyaluronic acid (HA) hydrogel platform to elucidate the impact of matrix stiffness on the behavior of MDA-MB-231Br cells, a brain metastasizing variant of the triple negative breast cancer line MDA-MB-231. We prepared HA hydrogels of varying stiffness (0.2-4.5 kPa) bracketing the brain relevant stiffness range to recapitulate the biophysical cues provided by brain extracellular matrix. In this system, we observed that the MDA-MB-231Br cell adhesion, spreading, proliferation, and migration significantly increased with the hydrogel stiffness. We also demonstrated that the stiffness based responses of these cells were mediated, in part, through the focal adhesion kinase-phosphoinositide-3 kinase pathway. This biomimetic material system with tunable stiffness provides an ideal platform to further the understanding of mechanoregulation associated with brain metastatic breast cancer cells. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1832-1841, 2018.

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Section: Resultsmentioning

confidence: 68%

The influence of matrix stiffness on the behavior of brain metastatic breast cancer cells in a biomimetic hyaluronic acid hydrogel platform

Narkhede

Crenshaw

Manning

et al. 2018

J Biomedical Materials Res

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“…During mammary ductal elongation and branching morphogenesis, the pubertal mammary epithelium invades into the fat pad stroma to form the gland that later evolves further during the menstrual cycle, and terminally differentiates/dedifferentiates during pregnancy, lactation and involution. This process involves significant regulation of the surrounding extracellular matrix (ECM) (Zhu et al, 2014;Gomes et al, 2015). Here, in areas of active cell division, hollow ducts are formed through luminal apoptosis, and cells undergo differentiation into luminal and basal mammary epithelial layers (Hinck & Silberstein, 2005;Ewald et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Complex signalling between the epithelium and the stroma orchestrates the mammary ductal outgrowth and branching through the adipose tissue (Sternlicht et al, 2006;Howard & Lu, 2014). This process involves significant regulation of the surrounding extracellular matrix (ECM) (Zhu et al, 2014;Gomes et al, 2015). Epithelial cell adhesion to the surrounding ECM via integrins, heterodimeric transmembrane adhesion receptors, plays an important role in mammary ductal outgrowth (Klinowska et al, 1999), in preserving the regenerative capacity of the mammary epithelium (Taddei et al, 2008), and during breast cancer invasion and metastasis (Levental et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

SHARPIN regulates collagen architecture and ductal outgrowth in the developing mouse mammary gland

et al. 2016

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SHARPIN is a widely expressed multifunctional protein implicated in cancer, inflammation, linear ubiquitination and integrin activity inhibition; however, its contribution to epithelial homeostasis remains poorly understood. Here, we examined the role of SHARPIN in mammary gland development, a process strongly regulated by epithelial-stromal interactions. Mice lacking SHARPIN expression in all cells (Sharpin), and mice with a stromal (S100a4-Cre) deletion of Sharpin, have reduced mammary ductal outgrowth during puberty. In contrast, Sharpin mammary epithelial cells transplanted in vivo into wild-type stroma, fully repopulate the mammary gland fat pad, undergo unperturbed ductal outgrowth and terminal differentiation. Thus, SHARPIN is required in mammary gland stroma during development. Accordingly, stroma adjacent to invading mammary ducts of Sharpin mice displayed reduced collagen arrangement and extracellular matrix (ECM) stiffness. Moreover, Sharpin mammary gland stromal fibroblasts demonstrated defects in collagen fibre assembly, collagen contraction and degradation in vitro Together, these data imply that SHARPIN regulates the normal invasive mammary gland branching morphogenesis in an epithelial cell extrinsic manner by controlling the organisation of the stromal ECM.

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“…This possibility has found much support through the literature both from the Bissell laboratory as well as others that there is physical linkage between the ECM through ECM receptors and the cytoskeleton, which in turn connects to the nuclear envelope receptors to physically couple to chromatin (Tapley and Starr, 2013). Even in traditional cell culture on flat substrata (2D cell culture), intriguing studies performed nearly 20 years ago made clear that the nucleus is mechanically linked to the plasma membrane through the cytoskeleton, and further, that under mechanical strain the nuclear morphology can be greatly altered (Bhat and Bissell, 2014;Hu et al, 2005;Maniotis et al, 1997;Osorio and Gomes, 2014;Zhu et al, 2014). These and a number of other studies raise the question 'what are the essential 3D architectural elements in the interconnected network of the nucleus, cytoskeleton and ECM in cells forming quiescent organotypic 3D structures that are akin to those in vivo?…”

Section: Introductionmentioning

confidence: 99%

Deep nuclear invaginations linked to cytoskeletal filaments: Integrated bioimaging of epithelial cells in 3D culture

Jorgens

Inman

Wojcik

et al. 2016

Journal of Cell Science

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The importance of context in regulation of gene expression is now an accepted principle; yet the mechanism by which the microenvironment communicates with the nucleus and chromatin in healthy tissues is poorly understood. A functional role for nuclear and cytoskeletal architecture is suggested by the phenotypic differences observed between epithelial and mesenchymal cells. Capitalizing on recent advances in cryogenic techniques, volume electron microscopy and super-resolution light microscopy, we studied human mammary epithelial cells in three-dimensional (3D) cultures forming growtharrested acini. Intriguingly, we found deep nuclear invaginations and tunnels traversing the nucleus, encasing cytoskeletal actin and/or intermediate filaments, which connect to the outer nuclear envelope. The cytoskeleton is also connected both to other cells through desmosome adhesion complexes and to the extracellular matrix through hemidesmosomes. This finding supports a physical and/or mechanical link from the desmosomes and hemidesmosomes to the nucleus, which had previously been hypothesized but now is visualized for the first time. These unique structures, including the nuclear invaginations and the cytoskeletal connectivity to the cell nucleus, are consistent with a dynamic reciprocity between the nucleus and the outside of epithelial cells and tissues.

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Extracellular matrix in mammary gland development and breast cancer progression

Cited by 33 publications

References 43 publications

The influence of matrix stiffness on the behavior of brain metastatic breast cancer cells in a biomimetic hyaluronic acid hydrogel platform

The influence of matrix stiffness on the behavior of brain metastatic breast cancer cells in a biomimetic hyaluronic acid hydrogel platform

SHARPIN regulates collagen architecture and ductal outgrowth in the developing mouse mammary gland

Deep nuclear invaginations linked to cytoskeletal filaments: Integrated bioimaging of epithelial cells in 3D culture

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