scholarly journals Dexamethasone Attenuates X-Ray-Induced Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle in Breast Tissue and Subsequent Breast Fibrosis

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 999 ◽  
Author(s):  
Guanmin Meng ◽  
Melinda Wuest ◽  
Xiaoyun Tang ◽  
Jennifer Dufour ◽  
Todd P.W. McMullen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Breast Tissue ◽  
Human Adipose Tissue ◽  
X Rays ◽  
Fat Pad ◽  
Breast Adipose Tissue ◽  
Mammary Fat Pad ◽  
Lpa1 Receptor ◽  
Breast Adipose ◽  
Radiation Induced

We recently showed that radiation-induced DNA damage in breast adipose tissue increases autotaxin secretion, production of lysophosphatidate (LPA) and expression of LPA1/2 receptors. We also established that dexamethasone decreases autotaxin production and LPA signaling in non-irradiated adipose tissue. In the present study, we showed that dexamethasone attenuated the radiation-induced increases in autotaxin activity and the concentrations of inflammatory mediators in cultured human adipose tissue. We also exposed a breast fat pad in mice to three daily 7.5 Gy fractions of X-rays. Dexamethasone attenuated radiation-induced increases in autotaxin activity in plasma and mammary adipose tissue and LPA1 receptor levels in adipose tissue after 48 h. DEX treatment during five daily fractions of 7.5 Gy attenuated fibrosis by ~70% in the mammary fat pad and underlying lungs at 7 weeks after radiotherapy. This was accompanied by decreases in CXCL2, active TGF-β1, CTGF and Nrf2 at 7 weeks in adipose tissue of dexamethasone-treated mice. Autotaxin was located at the sites of fibrosis in breast tissue and in the underlying lungs. Consequently, our work supports the premise that increased autotaxin production and lysophosphatidate signaling contribute to radiotherapy-induced breast fibrosis and that dexamethasone attenuated the development of fibrosis in part by blocking this process.

Multiple forms of 17β-hydroxysteroid oxidoreductase in human breast tissue

1989 ◽  
Vol 2 (1) ◽  
pp. 71-80 ◽  
Author(s):  
G.H. Tait ◽  
C.J. Newton ◽  
M.J. Reed ◽  
V.H.T. James
Keyword(s):  
Adipose Tissue ◽  
Breast Tissue ◽  
Soluble Form ◽  
Glandular Tissue ◽  
Human Breast ◽  
Human Breast Tissue ◽  
Molecular Weights ◽  
Breast Adipose Tissue ◽  
Breast Adipose ◽  
Membrane Bound

ABSTRACT 17β-Hydroxysteroid oxidoreductase, the enzyme that catalyses the interconversion of oestradiol and oestrone, is known to be present in human breast tissue. However, it is not known whether one or more forms of the enzyme is present. Homogenates of breast adipose tissue and breast glandular tissue were fractionated and fractions assayed in the oxidative direction with NAD+ and NADP+ as coenzymes, and in the reductive direction with NADH and NADPH as coenzymes. Ultracentrifugation of homogenates showed that there was membrane-bound activity and soluble activity. The soluble activity was due to a number of forms of the enzyme with different molecular weights, three in breast adipose tissue and two in breast glandular tissue, as shown by fractionation with (NH4)2SO4 followed by chromatography on Sephadex G-200. The forms of the enzyme isolated differed in their affinities for substrates and coenzymes and in the relative rates at which they catalysed the oxidative and reductive reactions. Preliminary experiments with breast tumours showed that they also contained membrane-bound activity and more than one soluble form of the enzyme.

scholarly journals Obesity and Breast Cancer: The Role of Crown-Like Structures in Breast Adipose Tissue in Tumor Progression, Prognosis, and Therapy

2020 ◽  
Vol 23 (3) ◽  
pp. 233 ◽  
Author(s):  
Sara Socorro Faria ◽  
Luís Henrique Corrêa ◽  
Gabriella Simões Heyn ◽  
Lívia Pimentel de Sant'Ana ◽  
Raquel das Neves Almeida ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Tumor Progression ◽  
Breast Adipose Tissue ◽  
Breast Adipose

scholarly journals Low Levels of Omega-3 Long-Chain Polyunsaturated Fatty Acids Are Associated with Bone Metastasis Formation in Premenopausal Women with Breast Cancer: A Retrospective Study

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3832
Author(s):  
Caroline Goupille ◽  
Philippe G. Frank ◽  
Flavie Arbion ◽  
Marie-Lise Jourdan ◽  
Cyrille Guimaraes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Bone Metastases ◽  
Premenopausal Women ◽  
Lymph Node Involvement ◽  
Axillary Lymph ◽  
Breast Adipose Tissue ◽  
Breast Adipose ◽  
Node Involvement ◽  
Low Levels

In the present study, we investigated various biochemical, clinical, and histological factors associated with bone metastases in a large cohort of pre- and postmenopausal women with breast cancer. Two hundred and sixty-one consecutive women with breast cancer were included in this study. Breast adipose tissue specimens were collected during surgery. After having established the fatty acid profile of breast adipose tissue by gas chromatography, we determined whether there were differences associated with the occurrence of bone metastases in these patients. Regarding the clinical and histological criteria, a majority of the patients with bone metastases (around 70%) had tumors with a luminal phenotype and 59% of them showed axillary lymph node involvement. Moreover, we found a negative association between the levels of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in breast adipose tissue and the development of bone metastases in premenopausal women. No significant association was observed in postmenopausal women. In addition to a luminal phenotype and axillary lymph node involvement, low levels of n-3 LC-PUFA in breast adipose tissue may constitute a risk factor that contributes to breast cancer bone metastases formation in premenopausal women.

scholarly journals Persistent Organic Pollutants and Breast Cancer: A Systematic Review and Critical Appraisal of the Literature

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1063 ◽  
Author(s):  
Kaoutar Ennour-Idrissi ◽  
Pierre Ayotte ◽  
Caroline Diorio
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Adipose Tissue ◽  
Organic Pollutants ◽  
Persistent Organic Pollutants ◽  
Cancer Incidence ◽  
Breast Cancer Incidence ◽  
Epidemiological Studies ◽  
Breast Adipose Tissue ◽  
Breast Adipose

Persistent organic pollutants (POPs) bioaccumulate in the food chain and have been detected in human blood and adipose tissue. Experimental studies demonstrated that POPs can cause and promote growth of breast cancer. However, inconsistent results from epidemiological studies do not support a causal relationship between POPs and breast cancer in women. To identify individual POPs that are repeatedly found to be associated with both breast cancer incidence and progression, and to demystify the observed inconsistencies between epidemiological studies, we conducted a systematic review of 95 studies retrieved from three main electronic databases. While no clear pattern of associations between blood POPs and breast cancer incidence could be drawn, POPs measured in breast adipose tissue were more clearly associated with higher breast cancer incidence. POPs were more consistently associated with worse breast cancer prognosis whether measured in blood or breast adipose tissue. In contrast, POPs measured in adipose tissue other than breast were inversely associated with both breast cancer incidence and prognosis. Differences in biological tissues used for POPs measurement and methodological biases explain the discrepancies between studies results. Some individual compounds associated with both breast cancer incidence and progression, deserve further investigation.

scholarly journals Novel semi-automated algorithm for high-throughput quantification of adipocyte size in breast adipose tissue, with applications for breast cancer microenvironment

Adipocyte ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 313-325
Author(s):  
Frank L. Lombardi ◽  
Naser Jafari ◽  
Kimberly A. Bertrand ◽  
Lauren J. Oshry ◽  
Michael R. Cassidy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
High Throughput ◽  
Cancer Microenvironment ◽  
Adipocyte Size ◽  
Automated Algorithm ◽  
Breast Adipose Tissue ◽  
Breast Adipose

scholarly journals SAT-126 Breast Adipose Tissue Extracellular Vesicles from Obese Women Increase Breast Cancer Aggressiveness - a Novel Mechanism for the Obesity-Breast Cancer Link

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Alberto Benito-Martin ◽  
Paul Paik ◽  
Malik Mushannen ◽  
Priya Bhardwaj ◽  
Sonya Oshchepkova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Adipose Tissue ◽  
Body Mass ◽  
Extracellular Vesicles ◽  
Human Breast ◽  
Mouse Xenograft Model ◽  
Breast Adipose Tissue ◽  
Breast Adipose

Abstract Background and Objectives: Breast cancer is among the most common cancer in women with 2.1 million new cases detected each year. Numerous studies have demonstrated a connection between body mass index (BMI) and cancer incidence, with obesity (BMI ≥ 30) being responsible for the development of at least 13 types of cancer, and 15% to 20% of total cancer-related mortality. The effects of extracellular vesicles (EVs) derived from the obese adipose tissue microenvironment on breast cancer have not yet been clearly elucidated. Methods: EVs were obtained from media conditioned with human breast adipose tissue from reduction mammoplasty (n=31). Women were healthy at the time of surgery and had no history of breast cancer. Patient samples were stratified based on their body mass index (BMI), with a BMI < 25 considered healthy and a BMI ≥ 25 considered overweight/obese. Breast adipose tissue-derived EVs (AT-EVs) were characterized (Quantitative Mass Spectrometry) and used to treat human breast cancer cell lines, including the ER+ MCF7 and triple negative breast cancer (TNBC) MDA-MB-231. Effects on cell proliferation and migration in vitro, and on tumor growth in a mouse xenograft model, were examined after long-term education with EVs. RNA sequencing was performed to investigate potential reprogramming induced by AT-EVs. Results: We found a positive correlation between protein amount per AT-EV and BMI. Quantitative proteomics of AT-EVs revealed 46 proteins that were significantly higher and 54 proteins that were significantly lower in specimens from women with a BMI ≥ 25 compared to women with a BMI < 25. AT-EVs from patients with a BMI ≥ 25 induced proliferation of MCF7 cells compared to AT-EVs from patients with a BMI < 25. Obese EVs induced a more aggressive phenotype in MDA-MB-231 cells, increasing their invasiveness in vitro. Obese EVs also increased the growth of MCF7 and MDA-MB-231 cells in vivo. Ingenuity pathway analysis of RNA-Seq data identified significant differences in mTOR signaling and canonical pathways associated with altered mitochondrial function. Conclusion: Our studies identify a novel mechanism to explain the obesity-breast cancer link in older women. Namely, that in obesity, the breast microenvironment produces EVs capable of reprogramming breast cancer cells to grow faster and be more aggressive. Identifying which cargo in breast AT-EV mediates these effects may provide new targets for intervention.

scholarly journals RANTES release by human adipose tissue in vivo and evidence for depot-specific differences

2009 ◽  
Vol 296 (6) ◽  
pp. E1262-E1268 ◽  
Author(s):  
Rana Madani ◽  
Kalypso Karastergiou ◽  
Nicola C. Ogston ◽  
Nazar Miheisi ◽  
Rahul Bhome ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Epicardial Adipose Tissue ◽  
Ex Vivo ◽  
Human Adipose Tissue ◽  
Fat Pad ◽  
Obese Subjects ◽  
Subcutaneous Adipose ◽  
Circulating Levels

Obesity is associated with elevated inflammatory signals from various adipose tissue depots. This study aimed to evaluate release of regulated on activation, normal T cell expressed and secreted (RANTES) by human adipose tissue in vivo and ex vivo, in reference to monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) release. Arteriovenous differences of RANTES, MCP-1, and IL-6 were studied in vivo across the abdominal subcutaneous adipose tissue in healthy Caucasian subjects with a wide range of adiposity. Systemic levels and ex vivo RANTES release were studied in abdominal subcutaneous, gastric fat pad, and omental adipose tissue from morbidly obese bariatric surgery patients and in thoracic subcutaneous and epicardial adipose tissue from cardiac surgery patients without coronary artery disease. Arteriovenous studies confirmed in vivo RANTES and IL-6 release in adipose tissue of lean and obese subjects and release of MCP-1 in obesity. However, in vivo release of MCP-1 and RANTES, but not IL-6, was lower than circulating levels. Ex vivo release of RANTES was greater from the gastric fat pad compared with omental ( P = 0.01) and subcutaneous ( P = 0.001) tissue. Epicardial adipose tissue released less RANTES than thoracic subcutaneous adipose tissue in lean ( P = 0.04) but not obese subjects. Indexes of obesity correlated with epicardial RANTES but not with systemic RANTES or its release from other depots. In conclusion, RANTES is released by human subcutaneous adipose tissue in vivo and in varying amounts by other depots ex vivo. While it appears unlikely that the adipose organ contributes significantly to circulating levels, local implications of this chemokine deserve further investigation.

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