scholarly journals Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer-Like Phenotype

2020 ◽  
Author(s):  
Gokhan Bahcecioglu ◽  
Xiaoshan Yue ◽  
Erin Howe ◽  
Ian Guldner ◽  
M. Sharon Stack ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Cells ◽  
Cell Motility ◽  
Cell Invasion ◽  
Protein Production ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Membrane Localization ◽  
Related Protein ◽  
E Cadherin

AbstractAge is a major risk factor for cancer. While the importance of age related genetic alterations in cells on cancer progression is well documented, the effect of aging extracellular matrix (ECM) has been overlooked. Here, we show for the first time that the aging breast ECM is sufficient to drive normal mammary epithelial cells (KTB21) to a more invasive and cancer-like phenotype, while promoting motility and invasiveness in MDA-MB-231 cells. E-cadherin membrane localization was lost in KTB21 cells cultured on the decellularized breast matrix from aged mice. Cell motility, cell invasion, and inflammatory cytokine and cancer-related protein production were increased significantly on the aged matrix, and many genes related to invasion were upregulated. Strikingly, we showed using single cell RNA sequencing that the aged matrix led to enrichment of a subpopulation of KTB21 cells that highly expressed epithelial-mesenchymal transition (EMT) and invasion-related genes. Lysyl oxidase (LOX) knockdown reverted the aged matrix-induced changes to the young levels; LOX siRNA treatment prevented the loss of E-cadherin membrane localization, and reduced cell motility, cell invasion, and cytokine and cancer-related protein production. Finally, we showed that the biophysical, mechanical and biochemical properties of the breast ECM were altered dramatically upon aging. Analyzing these factors and studying the differential response of the epithelial cells to young and aged ECMs could lead to identification of new targets for cancer treatment and could pave the way for the discovery of new therapeutic options.

Pattern of protein production by mammary epithelial cells cultured on membrane inserts

2001 ◽  
Vol 81 (2) ◽  
pp. 285-287 ◽  
Author(s):  
F. Cheli ◽  
A. Baldi ◽  
V. Dell’Orto ◽  
B. Zavizion ◽  
I. Politis
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Cells ◽  
Key Words ◽  
Protein Production ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Total Proteins ◽  
Bovine Mammary Epithelial Cells ◽  
Epithelial Resistance ◽  
Cells Cultured

Protein and plasminogen activator (PA) production by bovine mammary epithelial cells cultured on inserts and the effect of calcium were studied. The cells cultured on inserts coated with a bovine extracellular matrix established a stable trans-epithelial resistance, and secreted apically αs1-casein and PA. Extracellular calcium increased (P < 0.01) αs1-casein and total proteins, but not PA activity. Key words: Bovine mammary epithelial cells, inserts, differentiation

Effect of the extracellular matrix on plasminogen activator isozyme activities of human mammary epithelial cells in culture

1983 ◽  
Vol 3 (6) ◽  
pp. 982-990
Author(s):  
N S Yang ◽  
C Park ◽  
C Longley ◽  
P Furmanski
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Cells ◽  
Plasminogen Activator ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Collagen Gels ◽  
Human Mammary Epithelial Cells ◽  
Human Mammary Epithelial ◽  
Normal Human ◽  
Mcf 7

Multiple molecular forms of plasminogen activator were detected in normal human mammary epithelial cells in culture. Cells derived from (normal) breast mammoplasty specimens and grown on the surface of collagen gels exhibited three major classes of plasminogen activator isozymes (Mr = 100,000 [100K], 75,000 [75K], and 55,000 [55K]). The activity of the 100K and 75K isozymes was greatly reduced when the cells were grown on conventional tissue-culture-grade plastic surfaces. MCF-7, a human mammary carcinoma cell line, exhibited predominantly or exclusively the 55K isozyme, irrespective of the cell growth substratum. The activity of the 55K isozyme was more than twofold higher for MCF-7 cells grown on collagen gels than for cells grown on plastic. Progesterone, diethylstilbestrol, and estrogen stimulated the activity of the 55K isozyme of MCF-7 cells, but only when the cells were grown on a plastic surface. The plasminogen activator activities of the normal human mammary epithelial cells were not stimulated by these hormones, irrespective of the growth substratum. These results show that the expression of plasminogen activator isozymes by human mammary epithelial cells is subject to modulation by the extracellular matrix. Normal and malignant cells may differ in their responsiveness to these effects.

Extracellular Matrix Dependent Gene Regulation in Mammary Epithelial Cells

1995 ◽  
pp. 107-119 ◽  
Author(s):  
Christian Schmidhauser ◽  
Connie A. Myers ◽  
Romina Mossi ◽  
Gerald F. Casperson ◽  
Mina J. Bissell
Keyword(s):  
Extracellular Matrix ◽  
Gene Regulation ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial

Tenascin-C inhibits extracellular matrix-dependent gene expression in mammary epithelial cells. Localization of active regions using recombinant tenascin fragments

1995 ◽  
Vol 108 (2) ◽  
pp. 519-527 ◽  
Author(s):  
P.L. Jones ◽  
N. Boudreau ◽  
C.A. Myers ◽  
H.P. Erickson ◽  
M.J. Bissell
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Protein Synthesis ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Active Regions ◽  
Mammary Epithelial ◽  
Dependent Manner ◽  
Beta Casein ◽  
Casein Protein

The physiological role of tenascin in vivo has remained obscure. Although tenascin is regulated in a stage and tissue-dependent manner, knock-out mice appear normal. When tenascin expression was examined in the normal adult mouse mammary gland, little or none was present during lactation, when epithelial cells actively synthesize and secrete milk proteins in an extracellular matrix/lactogenic hormone-dependent manner. In contrast, tenascin was prominently expressed during involution, a stage characterized by the degradation of the extracellular matrix and the subsequent loss of milk production. Studies with mammary cell lines indicated that tenascin expression was high on plastic, but was suppressed in the presence of the laminin-rich, Engelbreth-Holm-Swarm (EHS) tumour biomatrix. When exogenous tenascin was added together with EHS to mammary epithelial cells, beta-casein protein synthesis and steady-state mRNA levels were inhibited in a concentration-dependent manner. Moreover, this inhibition by tenascin could be segregated from its effects on cell morphology. Using two beta-casein promoter constructs attached to the chloramphenicol acetyltransferase reporter gene we showed that tenascin selectively suppressed extracellular matrix/prolactin-dependent transcription of the beta-casein gene in three-dimensional cultures. Finally, we mapped the active regions within the fibronectin type III repeat region of the tenascin molecule that are capable of inhibiting beta-casein protein synthesis. Our data are consistent with a model where both the loss of a laminin-rich basement membrane by extracellular matrix-degrading enzymes and the induction of tenascin contribute to the loss of tissue-specific gene expression and thus the involuting process.

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