Myoepithelial cells: good fences make good neighbors

Adriance, Melissa C; Inman, Jamie L.; Petersen, Ole W.; Bissell, Mina J.

doi:10.1186/bcr1286

Cited by 215 publications

(219 citation statements)

References 93 publications

(76 reference statements)

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“…The dominant role of myoepithelial cells in guiding the selforganization of the mammary gland is particularly interesting in light of their hypothesized role as cellular tumor suppressors and master regulators of tissue architecture (36,37). Luminal epithelial cells or their progenitors are widely believed to be the cell of origin in most breast cancers (38).…”

Section: Discussionmentioning

confidence: 99%

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

Cerchiari

Garbe

Jee³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

107

120

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Developing tissues contain motile populations of cells that can selforganize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. The ducts and acini of the human mammary gland are prototypical heterogeneous and dynamic tissues comprising two concentrically arranged cell types. To investigate the consequences of cellular heterogeneity and plasticity on cell positioning in the mammary gland, we reconstituted its selforganization from aggregates of primary cells in vitro. We find that self-organization is dominated by the interfacial energy of the tissue-ECM boundary, rather than by differential homo-and heterotypic energies of cell-cell interaction. Surprisingly, interactions with the tissue-ECM boundary are binary, in that only one cell type interacts appreciably with the boundary. Using mathematical modeling and cell-type-specific knockdown of key regulators of cell-cell cohesion, we show that this strategy of self-organization is robust to severe perturbations affecting cell-cell contact formation. We also find that this mechanism of self-organization is conserved in the human prostate. Therefore, a binary interfacial interaction with the tissue boundary provides a flexible and generalizable strategy for forming and maintaining the structure of two-component tissues that exhibit abundant heterogeneity and plasticity. Our model also predicts that mutations affecting binary cell-ECM interactions are catastrophic and could contribute to loss of tissue architecture in diseases such as breast cancer.heterogeneity | cell sorting | differential adhesion | mammary | prostate S elf-organization is a process that contributes to pattern formation and repair at all scales of biological complexity. At the tissue scale, defining robust strategies of self-organization is critical for engineering functional tissues, as well as for understanding development and the breakdown of tissue structure during diseases such as cancer (1). During development, two or more populations of motile cells can self-organize into spatially ordered tissues by a process referred to as cell sorting (2-4). The outcome of cell sorting can be rationalized using physical models that invoke cell-type-specific differences in interfacial energies. Interfacial energies arise through the action of a contractile cell cortex coupled to adhesion molecules (e.g., cadherins) that link the cortices of neighboring cells and signal to modulate cortical tension at specific cellular interfaces (5). In general, the organization of a tissue after cell sorting corresponds to a configuration that maximizes the formation of the most energetically favorable (hereafter referred to as most cell-cell cohesive) † cellular interfaces (6). For example, with an intermediate level of heterotypic cell-cell cohesion the most self-cohesive cell type is typically found in the tissue core, with the le...

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Section: Discussionmentioning

confidence: 99%

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

Cerchiari

Garbe

Jee³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

107

120

View full text Add to dashboard Cite

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“…The question of how myoepithelial cells arise in the mammary gland has gained increased interest in light of accumulating findings that they play a pivotal role in the development and maintenance of breast tissue and that they may exert an important tumor suppressive role (reviewed in (30)). The cornerstone for successful studies concerning lineage relationships and the function of various cell types within the breast was the introduction and improvement of cell separation techniques.…”

Section: The Origin Of Myoepithelial Progenitor Cellsmentioning

confidence: 99%

Myoepithelial Cells: Their Origin and Function in Breast Morphogenesis and Neoplasia

Gudjonsson

Adriance

Sternlicht

et al. 2005

J Mammary Gland Biol Neoplasia

229

211

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The human breast epithelium is a branching ductal system composed of an inner layer of polarized luminal epithelial cells and an outer layer of myoepithelial cells that terminate in distally located terminal duct lobular units (TDLUs). While the luminal epithelial cell has received the most attention as the functionally active milk-producing cell and as the most likely target cell for carcinogenesis, attention on myoepithelial cells has begun to evolve with the recognition that these cells play an active part in branching morphogenesis and tumor suppression. A major question that has been the subject of investigation pertains to how the luminal epithelial and myoepithelial lineages are related and precisely how they arise from a common putative stem cell population within the breast. Equally important is the question of how heterotypic signaling occurs between luminal epithelial and surrounding myoepithelial cells in normal breast morphogenesis and neoplasia. In this review we discuss data from our laboratories and from others regarding the cellular origin of human myoepithelial cells, their function in maintaining tissue polarity in the normal breast, and their role during neoplasia.

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“…MCF-10A used to represent normal breast epithelium is a nontumorigenic cell line isolated from luminal ductal cells, the milk secreting cells of the mammary gland. 25 …”

Section: Cell Culturementioning

confidence: 99%

“…The negative control peptide corresponding to fibrinopeptide A induced minimal %FITC-Dextran Flux compared with Fg or peptide b 15-42 (#p < 0.0001); however, the 13% relative fluorescence was significant (-p 5 0.001) compared with basal levels that were 1% of intact Fg-induced permeability. Peptides missing b 15-17 residues (b [18][19][20][21][22][23][24][25][26][27][28][29][30][31] or b [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] ) or truncated at the C-terminus (b [15][16][17][18][19][20][21][22][23][24][25][26][27] (Fig. 2c).…”

Section: Fg-induced Ec Permeability Involves Fg-b 15-42 Sequences Andmentioning

confidence: 99%

“…14,[26][27][28] Control experiments indicated that Fg added to breast cancer or endothelial cells was not processed further by protease degradation or crosslinking to higher ordered structures (data not shown). Synthetic peptides corresponding to the Fg b-chain primary structure were custom synthesized as previously described, 11 and include b , b [15][16][17][18][19][20][21][22][23][24][25][26][27] , b 18-31 and b [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] (Table I). Fibrinopeptide A (Bachem) was used as a nonspecific peptide for permeability studies.…”

Section: Fibrinogen Purification and Synthetic Peptidesmentioning

confidence: 99%

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The VE‐cadherin binding domain of fibrinogen induces endothelial barrier permeability and enhances transendothelial migration of malignant breast epithelial cells

Sahni

Arévalo

Sahni

et al. 2009

Intl Journal of Cancer

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Fibrin deposition and exudation of plasma fibrinogen (Fg) have long been recognized as hallmarks of inflammation, cardiovascular disease and neoplasia. The Fg-b 15-42 domain binds to the endothelial cell adhesion molecule, VE-cadherin, promoting endothelial cell proliferation, angiogenesis and leukocyte diapedesis. Furthermore, spontaneous blood-borne and lymphatic metastasis of some types of tumor emboli requires plasma fibrin(ogen); however, the molecular mechanisms by which this occurs are poorly understood. We sought to determine whether Fg-b 15-42 and VEcadherin binding interactions promote endothelial barrier permeability and breast cancer cell transendothelial migration (TEM) using transwell insert culture systems. Synthetic peptides containing/missing residues b 15-17 critical for In 1865, Armand Trousseau reported the observation that patients with an increased incidence of coagulopathies would later manifest visceral malignancies, which became known as Trousseau's syndrome. Ironically, Trousseau diagnosed himself with his own syndrome in 1866 and died of gastric cancer the following year. Causal factors linked to the prothrombotic state of Trousseau's syndrome also facilitate cancer metastasis, including thrombin, tissue factor, selectins, platelets, endothelial cells (EC) and fibrin. 1 Deposition of fibrinogen (Fg) 5 and fibrin commonly occurs within the stroma of most solid tumors, 2 and elevated levels of plasma Fg and fibrin degradation products (FDPs) correlate positively with lymph node involvement and metastasis of colon, ovarian, lung and breast cancers. 1 Studies by Degen and co-workers 3-5 have firmly established that plasma fibrin(ogen) and platelets play critical roles in spontaneous cancer metastasis through both the circulation and lymphatic systems, in part by protecting tumor cells from natural killer cell-mediated lysis.Expression of interleukin (IL)-6 during systemic inflammation upregulates expression of specific plasma proteins in the liver, including Fg. 6 Excessive fibrin deposition is accompanied by local expression of proinflammatory mediators, vascular leakage, and inflammatory cell recruitment and activation leading to amplification of the inflammatory response. 2,7,8 Residues 15-42 on the b chain of Fg have been implicated in functional attributes ascribed to fibrin(ogen). Although the primary structure of fibrinopeptide B (FPB) is poorly conserved across species, the fibrin b 15-42 domain is highly conserved, implying evolutionary conservation of function. 9 The b 15-42 region constitutes a cryptic domain in soluble Fg that is exposed in fibrin after thrombin cleavage. 10 Newly exposed residues, b15-GHRP-18, promote lateral aggregation of fibrin monomers during polymerization and insoluble clot formation in secondary hemostasis. 10 Furthermore, exposure of the b 15-42 domain mediates fibrin binding to EC surfaces, 11 promotes EC adhesion and spreading, 12 and stimulates proliferation of EC, fibroblasts and cancer cells. 13,14 Cadherins mediate homophilic cell-cell adhesion...

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Myoepithelial cells: good fences make good neighbors

Cited by 215 publications

References 93 publications

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

Myoepithelial Cells: Their Origin and Function in Breast Morphogenesis and Neoplasia

The VE‐cadherin binding domain of fibrinogen induces endothelial barrier permeability and enhances transendothelial migration of malignant breast epithelial cells

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