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Estrogen Receptor Macrophages Breast Cancer

Ernesto Cortes, Muge Sarper, Benjamin Robinson, Dariusz Lachowski, Antonios Chronopoulos, Stephen D Thorpe, David A Lee, Armando E Del Río Hernández
The mechanical properties of the tumor microenvironment are emerging as attractive targets for the development of therapies. Tamoxifen, an agonist of the G protein-coupled estrogen receptor (GPER), is widely used to treat estrogen-positive breast cancer. Here, we show that tamoxifen mechanically reprograms the tumor microenvironment through a newly identified GPER-mediated mechanism. Tamoxifen inhibits the myofibroblastic differentiation of pancreatic stellate cells (PSCs) in the tumor microenvironment of pancreatic cancer in an acto-myosin-dependent manner via RhoA-mediated contractility, YAP deactivation, and GPER signaling...
December 11, 2018: EMBO Reports
Marcelo Sobral-Leite, Koen Van de Vijver, Magali Michaut, Rianne van der Linden, Gerrit K J Hooijer, Hugo M Horlings, Tesa M Severson, Anna Marie Mulligan, Nayana Weerasooriya, Joyce Sanders, Annuska M Glas, Diederik Wehkamp, Lorenza Mittempergher, Kelly Kersten, Ashley Cimino-Mathews, Dennis Peters, Erik Hooijberg, Annegien Broeks, Marc J van de Vijver, Rene Bernards, Irene L Andrulis, Marleen Kok, Karin E de Visser, Marjanka K Schmidt
To better understand the expression pattern of programmed death-ligand 1 (PD-L1) expression in different breast cancer types, we characterized PD-L1 expression in tumor and tumor-infiltrating immune cells, in relation to mutation rate, BRCA1 -like status and survival. We analyzed 410 primary treatment-naive breast tumors comprising 162 estrogen receptor-positive (ER+) and HER2-, 101 HER2+ and 147 triple-negative (TN) cancers. Pathologists quantified tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in tumor cells and TILs using whole slides and tissue microarray...
2018: Oncoimmunology
Lishan Zhang, Ming Liu, Jinglei Liu, Xingkai Li, Ming Yang, Benhua Su, Yanliang Lin
27-Hydroxycholesterol (27-HC) has been implicated in the pathological process of estrogen receptor positive breast cancer. However, the role of 27-HC in lung adenocarcinoma is still unclear. Because bone metastasis is a main reason for the high mortality of lung adenocarcinoma, this study aimed to investigate the effect of 27-HC on osteoclastogenesis in lung adenocarcinoma microenvironment. The results showed that the conditioned media (CM) from lung adenocarcinoma cells cocultured with macrophages promoted osteoclast differentiation, which was enhanced by 27-HC...
December 3, 2018: Journal of Cellular Physiology
Min Yao, Wei Fang, Curtis Smart, Qingting Hu, Shixia Huang, Nehemiah Alvarez, Patrick Fields, Nikki Cheng
Basal-like breast cancers are an aggressive breast cancer subtype, which often lack estrogen receptor, progesterone receptor and Her2 expression, and are resistant to anti-hormonal and targeted therapy, resulting in few treatment options. Understanding the underlying mechanisms that regulate progression of basal-like breast cancers would lead to new therapeutic targets and improved treatment strategies. Breast cancer progression is characterized by inflammatory responses, regulated in part by chemokines. The CCL2/CCR2 chemokine pathway is best known for regulating breast cancer progression through macrophage dependent mechanisms...
November 16, 2018: Molecular Cancer Research: MCR
Taryn L Cranford, Kandy T Velázquez, Reilly T Enos, Alexander T Sougiannis, Jackie E Bader, Meredith S Carson, Rebecca R Bellone, Ioulia Chatzistamou, Mitzi Nagarkatti, E Angela Murphy
Clinical studies provide strong evidence that obesity and associated adipose tissue (AT) inflammation are risk factors for breast cancer (BrCA); however, mechanistic knowledge of the interaction of obesity, BrCA, and menopausal status has proven to be not only lacking, but contradictory. Obesity-induced inflammation and elevated biosynthesis of estrogens, through aromatase-mediated metabolism of precursors, have been linked with hormone receptor positive (HP) postmenopausal BrCA but not previously associated with premenopausal BrCA risk...
November 2, 2018: Cancer Biology & Therapy
Laura W Bowers, Claire G Lineberger, Nikki A Ford, Emily L Rossi, Arunima Punjala, Kristina K Camp, Bruce K Kimler, Carol J Fabian, Stephen D Hursting
PURPOSE: Exposure to the polyphenolic plant lignan secoisolariciresinol diglucoside (SDG) and its metabolite enterolactone (ENL) has been associated with reduced breast cancer progression, particularly for estrogen receptor alpha (ERα)-negative disease, and decreased preclinical mammary tumor growth. However, while preclinical studies have established that SDG and ENL affect measures of progression in models of triple-negative breast cancer (TNBC, a subset of ERα-negative disease), the molecular mechanisms underlying these effects remain unclear...
October 26, 2018: Breast Cancer Research and Treatment
Wenyong Tan, Ming Yang, Hongli Yang, Fangbin Zhou, Weixi Shen
Neoadjuvant therapy (NAT) has been used increasingly in patients with locally advanced or early-stage breast cancer. However, the accurate evaluation and prediction of response to NAT remain the great challenge. Biomarkers could prove useful to identify responders or nonresponders, or even to distinguish between early and delayed responses. These biomarkers could include markers from the tumor itself, such as versatile proteins, genes, and ribonucleic acids, various biological factors or peripheral blood cells, and clinical and pathological features...
2018: Cancer Management and Research
Pengzhi Dong, Bing Yu, Lanlan Pan, Xiaoxuan Tian, Fangfang Liu
Purpose: Triple-negative breast cancer refers to breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (Her2). This study aimed to identify the key pathways and genes and find the potential initiation and progression mechanism of triple-negative breast cancer (TNBC). Methods: We downloaded the gene expression profiles of GSE76275 from Gene Expression Omnibus (GEO) datasets. This microarray Super-Series sets are composed of gene expression data from 265 samples which included 67 non-TNBC and 198 TNBC...
2018: BioMed Research International
Wentao Ning, Zhiye Hu, Chu Tang, Lu Yang, Silong Zhang, Chune Dong, Jian Huang, Hai-Bing Zhou
In this work, we developed a small library of novel OBHS-RES hybrid compounds with dual inhibition activities targeting both the estrogen receptor α (ERα) and NF-κB by incorporating resveratrol (RES), a known inhibitor of NF-κB, into a privileged indirect antagonism structural motif (OBHS, oxabicycloheptene sulfonate) of estrogen receptor (ER). The OBHS-RES conjugates could bind well to ER and showed remarkable ERα antagonistic activity, and they also exhibited excellent NO inhibition in macrophage RAW 264...
September 27, 2018: Journal of Medicinal Chemistry
Wenzhe Song, Parth Thakor, David A Vesey, Glenda C Gobe, Christudas Morais
Disparate roles exist for tumor-associated macrophages in breast cancer growth and progression. The aim of this study was to explore the influence of induced macrophages on the growth of breast cancer cells. THP-1 monocytes were differentiated to macrophages using phorbol 12-myristate 13-acetate. The effect of the medium from THP-1 monocytes or macrophage-conditioned medium (MφCM) on MCF-7 (estrogen receptor and progesterone-positive positive) and MDA-MB-231 (MB; triple-negative) breast cancer cells was determined at 24 h, 48 h and 72 h...
October 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Lirit N Franks, Benjamin M Ford, Toshifumi Fujiwara, Haibo Zhao, Paul L Prather
Selective estrogen receptor modulators (SERMs) target estrogen receptors (ERs) to treat breast cancer and osteoporosis. Several SERMs exhibit anti-cancer activity not related to ERs. To discover novel anti-cancer drugs acting via ER-independent mechanisms, derivatives of the SERM tamoxifen, known as the "ridaifen" compounds, have been developed that exhibit reduced or no ER affinity, while maintaining cytotoxicity. Tamoxifen and other SERMs bind to cannabinoid receptors with moderate affinity. Therefore, ER-independent effects of SERMs might be mediated via cannabinoid receptors...
June 12, 2018: Toxicology and Applied Pharmacology
Erin D Giles, Sonali Jindal, Elizabeth A Wellberg, Troy Schedin, Steven M Anderson, Ann D Thor, Dean P Edwards, Paul S MacLean, Pepper Schedin
BACKGROUND: Obesity and type II diabetes are linked to increased breast cancer risk in postmenopausal women. Patients treated with the antidiabetic drug metformin for diabetes or metabolic syndrome have reduced breast cancer risk, a greater pathologic complete response to neoadjuvant therapy, and improved breast cancer survival. We hypothesized that metformin may be especially effective when targeted to the menopausal transition, as this is a lifecycle window when weight gain and metabolic syndrome increase, and is also when the risk for obesity-related breast cancer increases...
June 14, 2018: Breast Cancer Research: BCR
Anbok Lee, Kyu Yeoun Won, Sung-Jig Lim, Sun Young Cho, Sang-Ah Han, SaeGwang Park, Jeong-Yoon Song
Many studies have reported that Aldehyde dehydrogenase 1 (ALDH1) and tumor-infiltrating lymphocytes (TIL) are related to breast cancer prognosis. However, the clinical significance of ALDH1 and tumor-infiltrating immune cells in breast cancer has not been fully investigated in patients who received neoadjuvant chemotherapy (NAC). We studied the significance of the expression of ALDH1 and the population of TIL for predicting the prognosis and chemotherapeutic response of patients with breast cancer who had received NAC...
May 2018: Pathology, Research and Practice
Yoon Jin Cha, Eun-Sol Kim, Ja Seung Koo
PURPOSE: We aimed to evaluate macrophage infiltration and to identify the status of crown-like structures (CLSs) in mammary adipose tissue of human breast tissue in cases with and without breast cancer. METHODS: Breast adipose tissue was obtained from reduction mammoplasty (N = 56, Group 1), non-neoplastic breast tissue of breast cancer patients (N = 84, Group 2), and breast cancer with adipose stroma (N = 140, Group 3). Immunohistochemical staining of CD68 and CD163 was performed, and the infiltrating macrophages and CLSs within breast adipose tissue were evaluated...
July 2018: Breast Cancer Research and Treatment
Neil M Iyengar, I-Chun Chen, Xi K Zhou, Dilip D Giri, Domenick J Falcone, Lisle A Winston, Hanhan Wang, Samantha Williams, Yen-Shen Lu, Tsu-Hsin Hsueh, Ann-Lii Cheng, Clifford A Hudis, Ching-Hung Lin, Andrew J Dannenberg
Obesity is associated with white adipose tissue (WAT) inflammation in the breast, elevated levels of the estrogen biosynthetic enzyme, aromatase, and systemic changes that predispose to breast cancer development. We examined whether WAT inflammation and its associated systemic effects correlate with body fat levels in an Asian population where body mass index (BMI) is not an accurate assessment of obesity and cancer risk. We also investigated whether biologic differences could account for the greater proportion of premenopausal estrogen receptor (ER)-positive breast cancer in Asian versus Western countries...
April 2018: Cancer Prevention Research
Ryuji Ohashi, Keiko Yanagihara, Shigeki Namimatsu, Takashi Sakatani, Hiroyuki Takei, Zenya Naito, Akira Shimizu
Breast carcinoma with osteoclast-like giant cells (OGCs) is a rare tumor; however, their clinicopathological aspects remain unclear. We described the clinicopathological characteristics of 8 patients with breast carcinoma with OGCs. Immuno-phenotypes of the OGCs were comparatively examined with that of foreign body giant cells (FBGCs) in 4 cases of granulomatous reaction (GR) without cancerous elements. In most cancers, tumors displayed cribriform and tubular growth patterns. Three cases showed moderate to high nuclear grade, while all the other tumors had low nuclear grade...
February 2018: Pathology, Research and Practice
Hidetoshi Mori, Jane Q Chen, Robert D Cardiff, Zsófia Pénzváltó, Neil E Hubbard, Louis Schuetter, Russell C Hovey, Josephine F Trott, Alexander D Borowsky
BACKGROUND: Stat1 gene-targeted knockout mice (129S6/SvEvTac-Stat1 tm1Rds ) develop estrogen receptor-positive (ER+ ), luminal-type mammary carcinomas at an advanced age. There is evidence for both host environment as well as tumor cell-intrinsic mechanisms to initiate tumorigenesis in this model. In this report, we summarize details of the systemic and mammary pathology at preneoplastic and tumor-bearing time points. In addition, we investigate tumor progression in the 129:Stat1 -/- host compared with wild-type 129/SvEv, and we describe the immune cell reaction to the tumors...
September 2, 2017: Breast Cancer Research: BCR
Rispah T Sawe, Simeon K Mining, Ayub V Ofulla, Kirtika Patel, Bernard Guyah, David Chumba, Jenifer R Prosperi, Maggie Kerper, Zonggao Shi, Mayra Sandoval-Cooper, Katherine Taylor, Sunil Badve, M Sharon Stack, Laurie E Littlepage
BACKGROUND: Tumors commonly are infiltrated by leukocytes, or tumor infiltrating leukocytes (TILs). It remains unclear, however, if the density and type of individual TILs has a direct or simply correlative role in promoting poor prognosis in breast cancer patients. Breast cancer in Kenyan women is aggressive with presentation at a young age, with advanced grade (grade III), large tumor size (>2.0 cm), and poor prognosis. We previously observed that the tumors were predominantly estrogen receptor positive (ER+) but also included both a high percentage of triple negative tumors and also increased immune cell infiltration within the tumors...
2017: Tropical Medicine and Health
Mariko Okamoto, Takuto Suzuki, Yoichi Mizukami, Teruo Ikeda
The female sex hormone estrogen exerts anti-inflammatory effects. The G-protein-coupled estrogen receptor (GPER) has been recently identified as a novel membrane-type estrogen receptor that can mediate non-genomic estrogenic effects on many cell types. We previously demonstrated that GPER inhibits tumor necrosis factor alpha-induced expression of interleukin 6 (IL-6) through repression of nuclear factor-kappa B (NF-κB) promoter activity using human breast cancer cells. Although several reports have indicated that GPER suppresses Toll-like receptor-induced inflammatory cytokine expression in macrophages, the molecular mechanisms of the inhibition of cytokine production via GPER remain poorly understood...
November 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
Yuko Miyasato, Takuya Shiota, Koji Ohnishi, Cheng Pan, Hiromu Yano, Hasita Horlad, Yutaka Yamamoto, Mutsuko Yamamoto-Ibusuki, Hirotaka Iwase, Motohiro Takeya, Yoshihiro Komohara
Recent studies have indicated the clinical significance of tumor-associated macrophages (TAM) in several malignant tumors including breast cancer. Although recent studies have focused on CD68-positive or CD163-positive TAM in breast cancer, no study has investigated the significance of CD204-positive TAM in breast cancer. We found that CD204 expression on macrophages was evaluated following stimulation with the conditioned medium (CM) of breast cancer cell lines. Paraffin sections of 149 breast cancer samples which were diagnosed as invasive ductal carcinoma were immunohistochemically analyzed for CD68, CD163 and CD204 expression...
August 2017: Cancer Science
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