scholarly journals Associations of Biomarkers of Inflammation and Breast Cancer in the Breast Adipose Tissue of Women with Combined Measures of Adiposity

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Sue-Ling Chang ◽  
André Tchernof ◽  
Francine Durocher ◽  
Caroline Diorio

Background. Mechanisms underlying the obesity-breast cancer link involve inflammation but need to be elucidated. Determining obesity by combining body mass index (BMI) with the waist circumference (WC) may clarify the role of inflammatory and hormonally related markers in breast cancer. We examined the effect of combining adiposity indices (BMI/WC) with the gene expression of several biomarkers involved in breast cancer. Methods. Expression of cytochrome P450 family 19 subfamily A member 1 (CYP19A1), estrogen receptor-alpha (ER-α), allograft inflammatory factor 1 (AIF1), cyclooxygenase-2 (COX2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and leptin (LEP) in 141 adipose breast tissues was quantified using qPCR method. BMI and WC were measured by a trained nurse and categorized using the median split, BMILOWCLO, BMILOWCHI, BMIHIWCLO, and BMIHIWCHI. Results. Gene expression of IL-6 (3-fold), TNF-α (2-fold), and LEP (2-fold) was higher in the breast adipose tissue of women with high WC regardless of BMI, that is, BMILOWCHI and BMIHIWCHI women (all P  < 0.01). Compared to BMILOWCLO women, gene expression of CYP19A1, COX2, and AIF1 was increased by two-fold in breast adipose tissue of BMIHIWCHI women ( P  < 0.10). ER-α was not different across adiposity categories. Conclusions. The expression of some biomarkers, particularly those related to inflammation, is elevated in breast adipose tissue of women with a high WC independent of BMI. Obesity monitoring should also include women with normal or low BMI, but with central adiposity.

Author(s):  
Nasser M. Al-Dagheri ◽  
Assim A. Alfadda ◽  
Reem M. Sallam ◽  
Philip G. McTernan ◽  
Lotfi S. Bin Dahman

Central adiposity is one of the significant determinants of obesity-related hypertension risk, which may arise due to the abdominal fat depot's pathogenic inflammatory nature. Pro-inflammatory cytokines and adipokines up-regulation through nuclear factor-kappa B (NF-&kappa;B) activation in adipose tissue has been considered an essential function in the pathogenesis of obesity-related hypertension. This study aimed to ascertain the NF-&kappa;B inhibitor (SN50) effect on TNF-&alpha; and angiotensinogen (AGT) secretion and expression in mediating the anti-inflammatory effect through its impact on NF-&kappa;B activity in humans adipose tissue. Primary human adipocytes were isolated from 20 subjects among 10 overweight and 10 obese with and without hypertension and treated with 10ng/ml LPS in the presence and absence of NF-&kappa;B inhibitor, SN50 (50&mu;g/ml). TNF-&alpha; secretion and NF-&kappa;B p65 activity were detected in supernatants extracted from cultured cells treated and untreated with LPS (10ng/ml) and SN50 (50&mu;g/ml) using enzyme-linked immunosorbent assay (ELISA). The western blot technique detected the protein of NF-&kappa;B p65 and AGT. Gene expression of TNF-&alpha; and AGT was detected in cells and performed using quantitative real-time polymerase chain reaction (RT-PCR). Treatment of AbdSc adipocytes with LPS (10ng/ml) caused a significant increase in NF-&kappa;B p65 among overweight and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. In contrast, SN50-NF-&kappa;B inhibitor causes a reduction of NF-&kappa;B p65 in overweight (P= &lt;0.001) and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. Treatment of AbdSc adipocytes with 10ng/ml LPS caused a significant increase in TNF-&alpha; secretion in overweight and obese subjects at all-time points (P= &lt;0.001), whereas SN50 leads to a decrease in TNF-&alpha; secretion at 3 and 12 hours incubation. Treatment of AbdSc adipocytes with LPS (10ng/ml) caused increased TNF-&alpha; and AGT gene expression twofold compared with untreated cells, whereas, in the presence of SN50, it reduces mRNA AGT levels in both groups. Taken together, these adipokines with NF-&kappa;B activation may represent essential biomarkers to evaluate hypertension risk and to provide insight into the pathogenesis of obesity-related hypertension.


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 ◽  
...  

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3832
Author(s):  
Caroline Goupille ◽  
Philippe G. Frank ◽  
Flavie Arbion ◽  
Marie-Lise Jourdan ◽  
Cyrille Guimaraes ◽  
...  

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.


Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1063 ◽  
Author(s):  
Kaoutar Ennour-Idrissi ◽  
Pierre Ayotte ◽  
Caroline Diorio

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.


Adipocyte ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 313-325
Author(s):  
Frank L. Lombardi ◽  
Naser Jafari ◽  
Kimberly A. Bertrand ◽  
Lauren J. Oshry ◽  
Michael R. Cassidy ◽  
...  

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Alberto Benito-Martin ◽  
Paul Paik ◽  
Malik Mushannen ◽  
Priya Bhardwaj ◽  
Sonya Oshchepkova ◽  
...  

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 &lt; 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 &lt; 25. AT-EVs from patients with a BMI ≥ 25 induced proliferation of MCF7 cells compared to AT-EVs from patients with a BMI &lt; 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.


1996 ◽  
Vol 7 (6) ◽  
pp. 591-595 ◽  
Author(s):  
Zhenrong Zhu ◽  
Markku Parviainen ◽  
Satu M�nnist� ◽  
Pirjo Pietinen ◽  
Matti Eskelinen ◽  
...  

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