scholarly journals ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix

2003 ◽  
Vol 163 (3) ◽  
pp. 583-595 ◽  
Author(s):  
Michele A. Wozniak ◽  
Radhika Desai ◽  
Patricia A. Solski ◽  
Channing J. Der ◽  
Patricia J. Keely
Keyword(s):  
Epithelial Cells ◽  
Three Dimensional ◽  
Collagen Gel ◽  
Collagen Matrix ◽  
Breast Epithelial Cell ◽  
Collagen Gels ◽  
Culture Dish ◽  
Breast Epithelial Cells ◽  
3D Collagen ◽  
Breast Epithelial

Breast epithelial cells differentiate into tubules when cultured in floating three-dimensional (3D) collagen gels, but not when the cells are cultured in the same collagen matrix that is attached to the culture dish. These observations suggest that the biophysical properties of collagenous matrices regulate epithelial differentiation, but the mechanism by which this occurs is unknown. Tubulogenesis required the contraction of floating collagen gels through Rho and ROCK-mediated contractility. ROCK-mediated contractility diminished Rho activity in a floating 3D collagen gel, and corresponded to a loss of FAK phosphorylated at Y397 localized to 3D matrix adhesions. Increasing the density of floating 3D collagen gels also disrupted tubulogenesis, promoted FAK phosphorylation, and sustained high Rho activity. These data demonstrate the novel finding that breast epithelial cells sense the rigidity or density of their environment via ROCK-mediated contractility and a subsequent down-regulation of Rho and FAK function, which is necessary for breast epithelial tubulogenesis to occur.

DETRENDED FLUCTUATION ANALYSIS OF CHROMATIN TEXTURE FOR DIAGNOSIS IN BREAST CYTOLOGY

Fractals ◽  
2002 ◽  
Vol 10 (01) ◽  
pp. 19-25 ◽  
Author(s):  
ANDREW J. EINSTEIN ◽  
HAI-SHAN WU ◽  
JUAN GIL
Keyword(s):  
Logistic Regression ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Detrended Fluctuation Analysis ◽  
Breast Epithelial Cell ◽  
Fluctuation Analysis ◽  
Scaling Exponent ◽  
Breast Epithelial Cells ◽  
Breast Epithelial ◽  
Detrended Fluctuation

Chromatin appearance in breast epithelial cells has been shown to have fractal properties, and detrended fluctuation analysis (DFA) is an effective method for characterizing the scaling in non-stationary fractal signals in terms of a scaling exponent. This study examines the use of DFA for the characterization of chromatin appearance in breast epithelial cells. Images of nuclei representative of fine-needle aspiration biopsies of the breast are characterized in terms of the scaling exponent for 19 patients with benign lesions and 22 patients with invasive ductal carcinoma. Characterizing patients by the standard deviations of the values of the scaling exponent for their representative nuclei, a statistically significant difference is noted between benign and malignant cases. This reflects that malignancies exhibit less variability in chromatin roughness than do benign cases. Previous logistic regression models for the diagnosis of breast epithelial cell lesions are improved upon by incorporating the standard deviation of the scaling exponent. Using leave-one-out cross-validation, the best logistic regression classifiers demonstrate a sensitivity of 95% and a specificity of 100%. A combination of DFA and lacunarity analysis is seen to provide the best approach to characterizing chromatin in breast epithelial cell nuclei.

scholarly journals Epithelia suspended in collagen gels can lose polarity and express characteristics of migrating mesenchymal cells.

1982 ◽  
Vol 95 (1) ◽  
pp. 333-339 ◽  
Author(s):  
G Greenburg ◽  
E D Hay
Keyword(s):  
Epithelial Cells ◽  
Cell Polarity ◽  
Three Dimensional ◽  
Collagen Gel ◽  
Mesenchymal Cells ◽  
Apical Surface ◽  
Collagen Gels ◽  
Mesenchymal Transformation

This study of epithelial-mesenchymal transformation and epithelial cell polarity in vitro reveals that environmental conditions can have a profound effect on the epithelial phenotype, cell shape, and polarity as expressed by the presence of apical and basal surfaces. A number of different adult and embryonic epithelia were suspended within native collagen gels. Under these conditions, cells elongate, detach from the explants, and migrate as individual cells within the three-dimensional lattice, a previously unknown property of well-differentiated epithelia. Epithelial cells from adult and embryonic anterior lens were studied in detail. Elongated cells derived from the apical surface develop pseudopodia and filopodia characteristic of migratory cells and acquire a morphology and ultrastructure virtually indistinguishable from that of mesenchymal cells in vivo. It is concluded from these experiments that the three-dimensional collagen gel can promote dissociation, migration, and acquisition of secretory organelles by differentiated epithelial cells, and can abolish the apical-basal cell polarity characteristic of the original epithelium.

scholarly journals Redox-dependent mechanisms of regulation of breast epithelial cell proliferation

2017 ◽  
Vol 63 (2) ◽  
pp. 159-164
Author(s):  
E.A. Stepovaya ◽  
E.V. Shakhristova ◽  
O.L. Nosareva ◽  
E.V. Rudikov ◽  
M.Y. Egorova ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Free Radical Oxidation ◽  
Redox Status ◽  
Stress Generation ◽  
Breast Epithelial Cell ◽  
Breast Epithelial Cells ◽  
Sh Group ◽  
Breast Epithelial ◽  
Number Of Cells

Activation of free radical oxidation in different cell types, including breast epithelial cells, may result in damage to macromolecules, in particular, proteins taking part in regulation of cell proliferation and apoptosis. The glutathione, glutaredoxin and thioredoxin systems play an essential role in maintaining intracellular redox homeostasis. Due to this fact, modulation of cellular redox status under the effect of an SH group inhibitor and an SH group protector may be used as a model for studying the role of redox proteins and glutathione in regulating cell proliferation in different pathological processes. In this study we have evaluated the state of the thioredoxin, glutaredoxin and glutathione systems as well as their role in regulating proliferation of HBL-100 breast epithelial cells under redox status modulation with N-ethylmaleimide (NEM) and 1,4-dithioerythriol (DTE). Modulating the redox status of breast epithelial cells under the effect of NEM and DTE influences the functional activity of glutathione-dependent enzymes, glutaredoxin, thioredoxin, and thioredoxin reductase through changes in the GSH and GSSG concentrations. In HBL-100 cells under redox-status modulation, we have found an increase in the number of cells in the S-phase of the cell cycle and a decrease in the number of cells in the G0/G1 and G2/М phases, as opposed to the values in the intact culture. The proposed model of proliferative activity of cells under redox status modulation may be used for development of new therapeutic approaches for treatment of diseases accompanied by oxidative stress generation.

scholarly journals Skin fibroblasts obtained from cancer patients display foetal-like migratory behaviour on collagen gels

1985 ◽  
Vol 73 (1) ◽  
pp. 235-244
Author(s):  
S.L. Schor ◽  
A.M. Schor ◽  
P. Durning ◽  
G. Rushton
Keyword(s):  
Cell Density ◽  
Normal Skin ◽  
Three Dimensional ◽  
Collagen Gel ◽  
Collagen Matrix ◽  
Skin Fibroblasts ◽  
Collagen Gels ◽  
Normal Range ◽  
Migratory Response ◽  
Fibroblast Migration

When plated on the surface of collagen gel substrata, all types of fibroblasts rapidly begin to migrate down into the three-dimensional collagen matrix. We have previously demonstrated that normal (adult and foreskin), foetal and transformed fibroblasts may be distinguished from each other by virtue of their differential migratory response to changes in cell density. The effects of cell density on fibroblast migration into the gel may be expressed by a single numerical value, the ‘cell density migration index’ (CDMI). We now present evidence that ostensibly normal skin fibroblasts obtained from the majority of patients we examined with carcinoma of the breast, malignant melanoma, familial polyposis coli, retinoblastoma and Wilms' tumours display aberrant CDMI values falling within the foetal range. Skin fibroblasts obtained from the majority of patients examined with genetic or chronic diseases (e.g. rheumatoid arthritis, Duchenne muscular dystrophy) displayed CDMI values falling within the normal range.

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