Radial Profile Analysis of Epithelial Polarity in Breast Acini: A Tool for Primary (Breast) Cancer Prevention

Manning, Lawton; Holmes, Julia; Bonin, Keith; Vidi, Pierre‐Alexandre

doi:10.3389/fmed.2019.00314

Cited by 6 publications

(7 citation statements)

References 50 publications

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“…These acini are growth-arrested with apical-basal polarity 28 , 29 , as in the human breast. After treating the acini with serum samples from the KTB, the structures were stained for the TJ marker ZO-1 and apical polarity was assessed by measuring the radial distribution of ZO-1 fluorescent signals 30 (Supplementary Fig. 3a, b ).…”

Section: Resultsmentioning

confidence: 99%

Reversion of breast epithelial polarity alterations caused by obesity

et al. 2023

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Molecular links between breast cancer risk factors and pro-oncogenic tissue alterations are poorly understood. The goal of this study was to characterize the impact of overweight and obesity on tissue markers of risk, using normal breast biopsies, a mouse model of diet-induced obesity, and cultured breast acini. Proliferation and alteration of epithelial polarity, both necessary for tumor initiation, were quantified by immunostaining. High BMI (>30) and elevated leptin were associated with compromised epithelial polarity whereas overweight was associated with a modest increase in proliferation in human and mice mammary glands. Human serum with unfavorable adipokine levels altered epithelial polarization of cultured acini, recapitulating the effect of leptin. Weight loss in mice led to metabolic improvements and restored epithelial polarity. In acini cultures, alteration of epithelial polarity was prevented by antioxidants and could be reverted by normalizing culture conditions. This study shows that obesity and/or dietary factors modulate tissue markers of risk. It provides a framework to set target values for metabolic improvements and to assess the efficacy of interventional studies aimed at reducing breast cancer risk.

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Section: Resultsmentioning

confidence: 99%

Reversion of breast epithelial polarity alterations caused by obesity

et al. 2023

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“…Frozen needle biopsy samples of normal human breast tissues were obtained from the Susan G. Komen Tissue Bank (KTB) at the IU Simon Cancer Center (IN, USA). We selected 40 tissue samples donated between 2009 and 2017, from three BMI groups (normal weight [18][19][20][21][22][23][24][25]; overweight [25.5-30]; obese [>30.5]) based on the following criteria: presence of epithelium evidenced in matching H&E, availability of frozen serum samples, no hormone replacement therapy (HRT) usage, no alcohol consumption, non-smoker donor, and pre-menopausal status.…”

Section: Procuration Of Human Breast Tissuementioning

confidence: 99%

“…Imaging of 96-well culture plates was automated using the WellNavigator function of CellSens (Olympus), with software-based autofocus on the DAPI staining. The RadialProfiler MATLAB software 24 (https://osf.io/e37st/) was used for automated analysis of apical polarity.…”

Section: Quantification Of Apical Polaritymentioning

confidence: 99%

“…These acini are growth-arrested with apical-basal polarity 22,23 , as in the human breast. After treating the acini with serum samples from the KTB, the structures were stained for the TJ marker ZO-1 and apical polarity was assessed by measuring the radial distribution of ZO-1 fluorescent signals 24 (Suppl. Fig.…”

Section: Serum With Metabolic Hallmarks Of Obesity Disrupts Epithelia...mentioning

confidence: 99%

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Reversion of the loss of breast epithelial polarity caused by obesity

Vidi

Holmes

Gaber

et al. 2022

Preprint

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Molecular links between breast cancer risk factors and pro-oncogenic tissue alterations are poorly understood. The goal of this study was to characterize the impact of overweight and obesity on tissue markers of risk, using normal breast biopsies, a mouse model of obesity, and cultured breast acini. Proliferation and disruption of epithelial polarity, both necessary for tumor initiation, were quantified by immunostaining. High BMI and elevated leptin were associated with compromised epithelial polarity whereas overweight was associated with proliferation in human and mice mammary glands. Human serum with unfavorable adipokine levels altered epithelial polarization of cultured acini, recapitulating the effect of leptin. Weight loss in mice led to metabolic improvements and restored epithelial polarity. In acini cultures, epithelial polarity loss was prevented by antioxidants and could be reverted by normalizing culture conditions. This study provides a framework to set target values for metabolic improvements and to assess the efficacy of interventional studies aimed at reducing breast cancer risk.

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“…Correct localization of apical and basal proteins is important for the physiological function of ductal, glandular, and tubular epithelial structures within organs [3][4][5][6][7] . Alterations to apical-basal polarity occur in several glandular cancers [8][9][10][11][12][13][14][15] . For example, tumor spheres with "inverted" or "apical-out" polarity have been recently shown to collectively metastasize 16 .…”

Section: Introductionmentioning

confidence: 99%

Rho activation drives luminal collapse and eversion in epithelial acini

Narayanan

Purkayastha

et al. 2022

Preprint

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Epithelial cells lining a gland and cells grown in a soft extracellular matrix polarize with apical proteins exposed to the lumen and basal proteins in contact with the extracellular matrix. Alterations to polarity, including an apical-out polarity, occur in human cancers. While some aberrant polarity states may result from altered protein trafficking, recent observations of an extraordinary tissue-level inside-out unfolding suggest an alternate pathway for altered polarity. Because mechanical alterations are common in human cancer including an upregulation of RhoA mediated actomyosin tension in acinar epithelia, we explored whether perturbing mechanical homeostasis could cause apical-out eversion. Acinar eversion was robustly induced by direct activation of RhoA or indirect activation of RhoA through blockage of β1 integrins, disruption of the LINC complex, oncogenic Ras activation, or Rac1 inhibition. Furthermore, laser ablation of a portion of the untreated acinus was sufficient to induce eversion. Analyses of acini revealed high curvature and low phosphorylated myosin in the apical cell surfaces relative to the basal surfaces. A vertex-based mathematical model which balances tension at cell-cell interfaces revealed a five-fold greater basal cell surface tension relative to the apical cell surface tension. The model suggests that the difference in surface energy between the apical and basal surfaces is the driving force for acinar eversion. Our findings raise the possibility that a loss of mechanical homeostasis may cause apical-out polarity states in human cancers.

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Radial Profile Analysis of Epithelial Polarity in Breast Acini: A Tool for Primary (Breast) Cancer Prevention

Cited by 6 publications

References 50 publications

Reversion of breast epithelial polarity alterations caused by obesity

Reversion of breast epithelial polarity alterations caused by obesity

Reversion of the loss of breast epithelial polarity caused by obesity

Rho activation drives luminal collapse and eversion in epithelial acini

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