Serum Amyloid A Is Associated with Obesity and Estrogen Receptor–Negative Tumors in Postmenopausal Women with Breast Cancer

Santana, Aline Barros; Gurgel, Maria Salete Costa; Montanari, Joelma Ferreira de Oliveira; Bonini, F.; Barros‐Mazon, Silvia de

doi:10.1158/1055-9965.epi-12-1020

Cited by 6 publications

(6 citation statements)

References 21 publications

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“…Serum of healthy donors expresses SAA at relatively low levels [49]. SAA protein levels were higher in patients with ER-negative breast tumors compared to those with ER-positive [50], supporting our findings of higher levels of SAA1/2 in TNBC (Figure 1 and Supplementary Figure 1). High levels of SAA were related to survival time of patients less than one year with breast invasive ductal carcinoma as a useful marker in BC recurrence [51].…”

Section: Discussionsupporting

confidence: 86%

Serum amyloid A predisposes inflammatory tumor microenvironment in triple negative breast cancer

et al. 2019

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Acute-phase proteins (APPs) are associated with a variety of disorders such as infection, inflammatory diseases, and cancers. The signature profile of APPs in breast cancer (BC) is poorly understood. Here, we identified serum amyloid A (SAA) for proinflammatory predisposition in BC through the signature profiles of APPs, interleukin (IL) and tumor necrosis factor (TNF) superfamily using publicly available datasets of tumor samples and cell lines. Triple-negative breast cancer (TNBC) subtype highly expressed SAA1/2 compared to HER2, luminal A (LA) and luminal B (LB) subtypes. IL1A, IL1B, IL8/CXCL8, IL32 and IL27RA in IL superfamily and CD70, TNFSF9 and TNFRSF21 in TNF superfamily were highly expressed in TNBC compared to other subtypes. SAA is restrictedly regulated by nuclear factor (NF)-κB and IL-1β, an NF-κB activator highly expressed in TNBC, increased the promoter activity of SAA1 in human TNBC MDA-MB231 cells. Interestingly, two κB-sites contained in SAA1 promoter were involved, and the proximal region (−96/−87) was more critical than the distal site (−288/−279) in regulating IL-1β-induced SAA1. Among the SAA receptors, TLR1 and TLR2 were highly expressed in TNBC. Cu-CPT22, TLR1/2 antagonist, abrogated IL-1β-induced SAA1 promoter activity. In addition, SAA1 induced IL8/CXCL8 promoter activity, which was partially reduced by Cu-CPT22. Notably, SAA1/2, TLR2 and IL8/CXCL8 were associated with a poor overall survival in mesenchymal-like TNBC. Taken together, IL-1-induced SAA via NF-κB-mediated signaling could potentiate an inflammatory burden, leading to cancer progression and high mortality in TNBC patients.

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Section: Discussionsupporting

confidence: 86%

Serum amyloid A predisposes inflammatory tumor microenvironment in triple negative breast cancer

et al. 2019

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“…Given the inflammatory state in obesity, a recent study investigating the relationship between SAA concentrations and tumor characteristics among overweight/obese and non-obese breast cancer patients reported higher SAA concentrations in patients with ER-negative tumors than those with ER-positive. 38 Additional investigations of the clinical role of SAA should be conducted including a larger sample size and prospective study design.…”

Section: Discussionmentioning

confidence: 99%

Weight Loss Intervention in Survivors of ER/PR-negative Breast Cancer

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Milliron

Hopkins

et al. 2014

Clin Med�Insights�Womens�Health

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Numerous studies have found that increased body size (weight or body mass index) is a risk factor for breast cancer development, recurrence, and death. The detrimental relationship between body size and breast cancer recurrence may be more pronounced among women with estrogen receptor (ER)/progesterone receptor (PR)-negative breast cancer. Considering the limited availability of treatments, and the association between body size and recurrence, alternative treatments are needed for ER/PR-negative breast cancer survivors, particularly overweight survivors. The objective of this pilot study was to examine the feasibility of a 12-week, multi-component meal-replacement weight loss intervention among overweight or obese ER/PR-negative breast cancer survivors; and to obtain preliminary data on changes in anthropometrics, biomarkers, and health-related quality of life (QOL). The 12-week intervention included a portion-controlled diet (including meal replacements) and a multi-component intervention (including behavioral techniques, diet modification, physical activity, and social support). The goal of the intervention was to help participants lose 5% or more of their initial weight by reducing their caloric intake and increasing their physical activity (to at least 15 minutes each day). Paired t-tests assessed changes in continuous measures. Body weight was measured weekly and mixed-model regression analysis assessed change in weight over time. Nineteen ER/PR-negative breast cancer survivors with a mean age of 59 years participated in the study. All but two of the participants completed the 12-week intervention. Women lost an average of 6.3 ± 4.9 kg (P < 0.001), equivalent to 7.5% of their baseline weight. There were significant reductions in waist circumference (P = 0.001), percent fat mass (P < 0.001), total cholesterol (P = 0.026), and triglycerides (P = 0.002); and improvements in health-related QOL (P = 0.017). Findings suggested that a meal-replacement weight loss approach among ER/PR-negative breast cancer survivors was feasible and was well received.

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“…Além disso, a SAA á capaz de condicionar o nicho tumoral pré-metastático facilitando o acúmulo de células mielóides, acelerando o recrutamento de células tumorais para o pulmão pré-metastático (Hiratsuka et al, 2008). Recentemente, Santana et al (2013) observaram que a SAA influencia no desenvolvimento do câncer de mama. Além disso, nódulos originados de cirrose alcoólica e que são positivos para SAA apresentam uma natureza neoplásica (Sasaki et al, 2014).…”

Section: Câncer Inflamação De Saaunclassified

Ação da proteína amiloide sérica A em melanomas

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Concentrações séricas basais da proteína amiloide sérica A (SAA) estão significativamente aumentadas em pacientes com câncer e alguns autores sugerem uma relação causal. Trabalho anterior do grupo mostrou que a SAA induz a proliferação de duas linhagens de glioblastoma humano e afeta os processos de invasividade in vitro, sustentando um papel pró-tumoral para esta proteína. Com base nesse trabalho, investigamos a abrangência dos efeitos de SAA para outro tipo de célula tumoral e para isso escolhemos um painel de linhagens de melanoma humano e uma linhagem primária obtida a partir de aspirado de linfonodo de paciente com melanoma, por nós isolada. Observamos que apesar da célula precursora de melanomas, isto é, melanócito, não produzir SAA, todas as linhagens de melanoma produziram a proteína e expressaram alguns dos seus receptores. Além disso, quando estas células foram estimuladas com SAA houve uma inibição da proliferação em tempos curtos de exposição (48 horas) e efeitos citotóxicos após um tempo maior (7 dias). A SAA também afetou processos de invasividade e a produção das citocinas IL-6, IL-8 e TNF-α. Aos avaliarmos o efeito da SAA na interação das células de melanoma com células do sistema imune, vimos que a SAA ativou uma resposta imune anti-tumoral aumentando a expressão de moléculas coestumolatórias, como CD69 e HLA-DR, e sua função citotóxica. Ainda, vimos que a produção de TNF-α, IFN-γ, IL-10, IL-1β e IL-8 estimuladas por SAA podem contribuir com os efeitos desta. De forma geral estes resultados nos levam a crer que a SAA tem atividade anti-tumoral em melanomas. Finalizando, com base na importância do desenvolvimento da resistência às terapias atuais para o melanoma, observamos que em células resistentes ao PLX4032, um inibidor de BRAF, os efeitos imunomodulatórios induzidos pela SAA estão abolidos, possivelmente identificando um novo componente da resistência.

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Serum Amyloid A Is Associated with Obesity and Estrogen Receptor–Negative Tumors in Postmenopausal Women with Breast Cancer

Cited by 6 publications

References 21 publications

Serum amyloid A predisposes inflammatory tumor microenvironment in triple negative breast cancer

Serum amyloid A predisposes inflammatory tumor microenvironment in triple negative breast cancer

Weight Loss Intervention in Survivors of ER/PR-negative Breast Cancer

Ação da proteína amiloide sérica A em melanomas

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