scholarly journals Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition

2002 ◽  
Vol 115 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Thorarinn Gudjonsson ◽  
Lone Rønnov-Jessen ◽  
René Villadsen ◽  
Fritz Rank ◽  
Mina J. Bissell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Basement Membrane ◽  
Specific Antigen ◽  
Myoepithelial Cells ◽  
Normal Breast ◽  
Breast Epithelial ◽  
Luminal Epithelial Cells ◽  
Laminin 1

The signals that determine the correct polarity of breast epithelial structures in vivo are not understood. We have shown previously that luminal epithelial cells can be polarized when cultured within a reconstituted basement membrane gel. We reasoned that such cues in vivo may be given by myoepithelial cells. Accordingly, we used an assay where luminal epithelial cells are incorrectly polarized to test this hypothesis. We show that culturing human primary luminal epithelial cells within collagen-I gels leads to formation of structures with no lumina and with reverse polarity as judged by dual stainings for sialomucin, epithelial specific antigen or occludin. No basement membrane is deposited, and β4-integrin staining is negative. Addition of purified human myoepithelial cells isolated from normal glands corrects the inverse polarity, and leads to formation of double-layered acini with central lumina. Among the laminins present in the human breast basement membrane (laminin-1, -5 and -10/11), laminin-1 was unique in its ability to substitute for myoepithelial cells in polarity reversal.Myoepithelial cells were purified also from four different breast cancer sources including a biphasic cell line. Three out of four samples either totally lacked the ability to interact with luminal epithelial cells, or conveyed only correction of polarity in a fraction of acini. This behavior was directly related to the ability of the tumor myoepithelial cells to produce α-1 chain of laminin. In vivo, breast carcinomas were either negative for laminin-1 (7/12 biopsies) or showed a focal, fragmented deposition of a less intensely stained basement membrane (5/12 biopsies). Dual staining with myoepithelial markers revealed that tumor-associated myoepithelial cells were either negative or weakly positive for expression of laminin-1, establishing a strong correlation between loss of laminin-1 and breast cancer. We conclude that the double-layered breast acinus may be recapitulated in culture and that one reason for the ability of myoepithelial cells to induce polarity is because they are the only source of laminin-1 in the breast in vivo. A further conclusion is that a majority of tumor-derived/-associated myoepithelial cells are deficient in their ability to impart polarity because they have lost their ability to synthesize sufficient or functional laminin-1. These results have important implications for the role of myoepithelial cells in maintenance of polarity in normal breast and how they may function as structural tumor suppressors.

scholarly journals Bringing androgens up a NOTCH in breast cancer

2014 ◽  
Vol 21 (4) ◽  
pp. T183-T202 ◽  
Author(s):  
Gerard A Tarulli ◽  
Lisa M Butler ◽  
Wayne D Tilley ◽  
Theresa E Hickey
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Normal Breast ◽  
Notch Signalling ◽  
Breast Development ◽  
Breast Epithelium ◽  
Breast Epithelial Cells ◽  
Androgen Action ◽  
Breast Epithelial

While it has been known for decades that androgen hormones influence normal breast development and breast carcinogenesis, the underlying mechanisms have only been recently elucidated. To date, most studies have focused on androgen action in breast cancer cell lines, yet these studies represent artificial systems that often do not faithfully replicate/recapitulate the cellular, molecular and hormonal environments of breast tumoursin vivo. It is critical to have a better understanding of how androgens act in the normal mammary gland as well as inin vivosystems that maintain a relevant tumour microenvironment to gain insights into the role of androgens in the modulation of breast cancer development. This in turn will facilitate application of androgen-modulation therapy in breast cancer. This is particularly relevant as current clinical trials focus on inhibiting androgen action as breast cancer therapy but, depending on the steroid receptor profile of the tumour, certain individuals may be better served by selectively stimulating androgen action. Androgen receptor (AR) protein is primarily expressed by the hormone-sensing compartment of normal breast epithelium, commonly referred to as oestrogen receptor alpha (ERa (ESR1))-positive breast epithelial cells, which also express progesterone receptors (PRs) and prolactin receptors and exert powerful developmental influences on adjacent breast epithelial cells. Recent lineage-tracing studies, particularly those focussed on NOTCH signalling, and genetic analysis of cancer risk in the normal breast highlight how signalling via the hormone-sensing compartment can influence normal breast development and breast cancer susceptibility. This provides an impetus to focus on the relationship between androgens, AR and NOTCH signalling and the crosstalk between ERa and PR signalling in the hormone-sensing component of breast epithelium in order to unravel the mechanisms behind the ability of androgens to modulate breast cancer initiation and growth.

scholarly journals Evidence for accelerated aging in mammary epithelia of women carrying germline BRCA1 or BRCA2 mutations

Nature Aging ◽  
2021 ◽  
Vol 1 (9) ◽  
pp. 838-849 ◽  
Author(s):  
Sundus F. Shalabi ◽  
Masaru Miyano ◽  
Rosalyn W. Sayaman ◽  
Jennifer C. Lopez ◽  
Tiina A. Jokela ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cancer Susceptibility ◽  
Breast Cancer Subtype ◽  
Accelerated Aging ◽  
Myoepithelial Cells ◽  
Normal Breast ◽  
Younger Women ◽  
Luminal And Myoepithelial Cells ◽  
Luminal Epithelial Cells

AbstractDuring aging in the human mammary gland, luminal epithelial cells lose lineage fidelity by expressing markers normally expressed in myoepithelial cells. We hypothesize that loss of lineage fidelity is a general manifestation of epithelia that are susceptible to cancer initiation. In the present study, we show that histologically normal breast tissue from younger women who are susceptible to breast cancer, as a result of harboring a germline mutation in BRCA1, BRCA2 or PALB2 genes, exhibits hallmarks of accelerated aging. These include proportionately increased luminal epithelial cells that acquired myoepithelial markers, decreased proportions of myoepithelial cells and a basal differentiation bias or failure of differentiation of cKit+ progenitors. High-risk luminal and myoepithelial cells are transcriptionally enriched for genes of the opposite lineage, inflammatory- and cancer-related pathways. We have identified breast-aging hallmarks that reflect a convergent biology of cancer susceptibility, regardless of the specific underlying genetic or age-dependent risk or the associated breast cancer subtype.

scholarly journals Expression of estrogen receptor β isoforms in normal breast epithelial cells and breast cancer: regulation by methylation

Oncogene ◽  
2003 ◽  
Vol 22 (48) ◽  
pp. 7600-7606 ◽  
Author(s):  
Chunyan Zhao ◽  
Eric W-F Lam ◽  
Andrew Sunters ◽  
Eva Enmark ◽  
Manuela Tamburo De Bella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Epithelial Cells ◽  
Normal Breast ◽  
Estrogen Receptor Β ◽  
Breast Epithelial Cells ◽  
Breast Epithelial ◽  
Normal Breast Epithelial Cells

scholarly journals TGF-β1 stimulates epithelial–mesenchymal transition and cancer-associated myoepithelial cell during the progression from in situ to invasive breast cancer

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Wang ◽  
Cong Xu ◽  
Xia Liu ◽  
Yang Yang ◽  
Lu Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Ductal Carcinoma ◽  
Myoepithelial Cells ◽  
Normal Breast ◽  
Emt Markers ◽  
Tgf Β1

Abstract Background The progression of ductal carcinoma in situ (DCIS) into invasive ductal carcinoma (IDC) is prevented by normal breast myoepithelial cells. Studies have suggested that EMT-associated genes were enriched in IDC in contrast to DCIS. This paper explored the relationship and potential mechanism between myoepithelial cells and EMT-associated genes in facilitating the transformation from DCIS to breast cancer. Methods EMT markers and myoepithelial phenotypic markers in IDC, DCIS, and healthy breast tissue were characterized using immunohistochemical assay. Both in vivo and in vitro models were created to mimic the various cell–cell interactions in the development of invasive breast cancer. Results We found that EMT markers were more abundant in invasive carcinomas than DCIS and adjacent normal breast tissue. Meanwhile, TGF-β1 regulated the morphology of MCF-7 (epithelial cells substitute) migration and EMT markers during the transformation from DCIS to invasive breast cancer. Additionally, TGF-β1 also regulated invasion, migration and cytokines secretion of MDA-MB-231 (myoepithelial cells substitute) and epithelial cells when co-cultured with MCF-7 both in vitro and in vivo. Conclusions In conclusion, these findings demonstrated that both EMT phenotypes and cancer-associated myoepithelial cells may have an impact on the development of invasive breast cancer.

Normal Breast Epithelial Cells Induce Apoptosis of MCF-7 Breast Cancer Cells through a p53-Mediated Pathway

2000 ◽  
Vol 3 (6) ◽  
pp. 338-344 ◽  
Author(s):  
Robert-Alain Toillon ◽  
Eric Adriaenssens ◽  
Danièle Wouters ◽  
Severine Lottin ◽  
Bénoni Boilly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Normal Breast ◽  
Breast Epithelial Cells ◽  
Breast Epithelial ◽  
Normal Breast Epithelial Cells ◽  
Mcf 7

Characterization of rat mammary cell types in primary culture: lectins and antisera to basement membrane and intermediate filament proteins as indicators of cellular heterogeneity

1985 ◽  
Vol 79 (1) ◽  
pp. 287-304
Author(s):  
M.J. Warburton ◽  
S.A. Ferns ◽  
C.M. Hughes ◽  
P.S. Rudland
Keyword(s):  
Membrane Proteins ◽  
Epithelial Cells ◽  
Basement Membrane ◽  
Intermediate Filament ◽  
Cell Types ◽  
Myoepithelial Cells ◽  
Epithelioid Cells ◽  
Intermediate Filament Proteins ◽  
Basement Membrane Proteins

Three morphologically distinct major cell types were observed in primary cultures obtained from the mammary parenchyma of glands from virgin rats. These cell types consisted of small cuboidal epithelial cells, larger epithelioid cells and elongated cells. We have investigated the distribution of the basement membrane proteins laminin and type IV collagen, and the intermediate filament proteins vimentin and prekeratin, in these three cell types using immunofluorescence techniques. Antisera to the basement membrane proteins stain the large epithelioid cells and the elongated cells, but do not stain the small cuboidal cells. Polyclonal antiserum to keratin stains all the small cuboidal and large epithelioid cells, but only a small subpopulation of the elongated cells. However, a monoclonal antibody to keratin, LP34, stains only the large cuboidal and a proportion of the elongated cells. Vimentin antiserum fails to stain the small cuboidal cells but stains all the large epithelioid and elongated cells. In addition, peanut lectin, which binds only to ductal lining epithelial cells in the virgin rat mammary gland in vivo after their treatment with neuraminidase, binds to the small cuboidal cells after neuraminidase treatment but not to the other cell types. However, Griffonia simplicifolia agglutinin I, which specifically stains myoepithelial cells in vivo, binds to the large epithelioid and elongated cells but not to the small cuboidal cells. These results suggest that the small cuboidal cells are related to mammary ductal epithelial cells whereas the large epithelial and elongated cells have some characteristics of myoepithelial cells.

scholarly journals Modelling and Validating Three-Dimensional Human Breast and Cancerous Human Breast Tissues In Vitro

2020 ◽  
pp. 1-9
Author(s):  
Anna Karolina Zuk ◽  
Anna Karolina Zuk ◽  
Beata Burczynska ◽  
Dong Li ◽  
Lucy Ghali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Smooth Muscle Actin ◽  
Three Dimensional ◽  
Myoepithelial Cells ◽  
In Vitro Models ◽  
Normal Breast ◽  
Human Breast ◽  
Mucin 1

In this study three dimensional (3-D) in vitro models of normal breast and breast cancer tissues were developed to mimic closely the in vivo tissue microenvironment and therefore providing reliable models for in vitro studies as well as testing of novel cancer therapies. Normal and cancerous human breast cell lines were used to construct 3-D artificial tissues, where de-epidermalised dermis (DED) was used as a scaffold for both models. Morphological analyses were conducted using haematoxylin and eosin staining. Biomarkers including keratin 5 and 19 as well as α smooth muscle actin and mucin 1 were used to confirm and validate the reliability of the proposed models using immunohistochemical techniques. Findings suggest that the 3-D in vitro models described in this work can serve as functional models of both human normal and cancerous breast tissues. Multiple structures similar to ducts and lobules of human breast in vivo were observed in 3-D in vitro models by the use of H&E, some breast cancer colonies seen in the cancerous 3-D model were similar to the ducto-lobular structures observed in normal 3-D model of the breast but the former cells were more loosely connected, irregular and largely disorganized. The established 3-D in vitro model of normal breast showed the development of ducto-lobular structures composed of an inner cell layer which was stained positive with α mucin 1 antibody, a biomarker that is characteristic for luminal cells; and also an outer basal layer of cells that was stained positive for α smooth muscle actin, a biomarker of myoepithelial cells.. Keratin staining in 3-D in vitro models also resembled the pattern observed in vivo where keratin 5 was detected in both luminal and myoepithelial cells of normal breast model (NTERT cells), whereas keratin 19 was present in breast cancer model (C2321 cells). These 3-D models successfully recapitulate both normal and pathological tissue architecture of breast tissue and has the potential for various applications in the evaluation of breast cancer progression and treatment.

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