Endocrine disruptors and the tumor microenvironment: A new paradigm in breast cancer biology

2017 ◽  
Vol 457 ◽  
pp. 13-19 ◽  
Author(s):  
Hope Burks ◽  
Nicholas Pashos ◽  
Elizabeth Martin ◽  
John Mclachlan ◽  
Bruce Bunnell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Endocrine Disruptors ◽  
Cancer Biology ◽  
New Paradigm

Stress sensing within the breast tumor microenvironment: how glucocorticoid receptors live in the moment

2021 ◽  
Author(s):  
Carlos Perez Kerkvliet ◽  
Thu H. Truong ◽  
Julie Hanson Ostrander ◽  
Carol A. Lange
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Signaling Pathways ◽  
Cancer Biology ◽  
Transcriptional Activity ◽  
Cellular Stress ◽  
Mapk Signaling ◽  
Cellular Growth ◽  
Steroid Hormone Receptors ◽  
Stress Signaling

Abstract The classification and treatment of breast cancer is largely defined by the expression of steroid hormone receptors (HRs), namely estrogen receptor (ER) and progesterone receptor (PR), and gene amplification/overexpression of human epidermal growth factor receptor 2 (HER2). More recently, studies of androgen receptor (AR), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR) have revealed that targeting these related HRs may be a promising strategy for a more personalized approach to the treatment of specific subtypes of HR+ breast cancer. For example, GR expression is associated with a good prognosis in ER+ breast cancer, but predicts poor prognosis in triple-negative breast cancer (TNBC). GR, like ER, PRs, and AR, is a ligand-activated transcription factor, but also has significant ligand-independent signaling activities. GR transcriptional activity is classically regulated by circulating glucocorticoids (GCs; ligand-dependent). Recent studies demonstrate that GR transcriptional activity is also regulated by a variety of cellular stress stimuli that input to GR Ser134 phosphorylation via rapid activation of the p38 mitogen activated protein kinase (MAPK) signaling pathway (ligand-independent). Furthermore, ligand-independent GR activation promotes feedforward signaling loops that mediate sustained activation of stress signaling pathways to drive advanced cancer biology (i.e. migration, invasion, chemoresistance, survival, and cellular growth). In this review, we will focus on the role of GR as a key sensor and mediator of physiologic and tumor microenvironment (TME)-derived cellular stress signaling in TNBC and discuss how targeting GR and/or associated signaling pathways may provide a strategy to inhibit deadly TNBC progression.

scholarly journals Bioengineering Models for Breast Cancer Research

2015 ◽  
Vol 9s2 ◽  
pp. BCBCR.S29424 ◽  
Author(s):  
Khadidiatou Guiro ◽  
Treena L. Arinzeh
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Biology ◽  
Three Dimensional ◽  
In Vivo Models ◽  
Culture Models ◽  
Approaches To Study ◽  
Cell Culture Models

Despite substantial advances in early diagnosis, breast cancer (BC) still remains a clinical challenge. Most BC models use complex in vivo models and two-dimensional monolayer cultures that do not fully mimic the tumor microenvironment. The integration of cancer biology and engineering can lead to the development of novel in vitro approaches to study BC behavior and quantitatively assess different features of the tumor microenvironment that may influence cell behavior. In this review, we present tissue engineering approaches to model BC in vitro. Recent advances in the use of three-dimensional cell culture models to study various aspects of BC disease in vitro are described. The emerging area of studying BC dormancy using these models is also reviewed.

The Role of Cytokines in Interactions of Mesenchymal Stem Cells and Breast Cancer Cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Hariharan Jayaraman ◽  
Nalinkanth V. Ghone ◽  
Ranjith Kumaran R ◽  
Himanshu Dashora
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cell Communication ◽  
Extra Cellular Matrix ◽  
Cytokine Signaling ◽  
Cellular Matrix

: Mesenchymal stem cells because of its high proliferation, differentiation, regenerative capacity, and ease of availability have been a popular choice in cytotherapy. Mesenchymal Stem Cells (MSCs) have a natural tendency to home in a tumor microenvironment and acts against it, owing to the similarity of the latter to an injured tissue environment. Several studies have confirmed the recruitment of MSCs by tumor through various cytokine signaling that brings about phenotypic changes to cancer cells, thereby promoting migration, invasion, and adhesion of cancer cells. The contrasting results on MSCs as a tool for cancer cytotherapy may be due to the complex cell to cell interaction in the tumor microenvironment, which involves various cell types such as cancer cells, immune cells, endothelial cells, and cancer stem cells. Cell to cell communication can be simple or complex and it is transmitted through various cytokines among multiple cell phenotypes, mechano-elasticity of the extra-cellular matrix surrounding the cancer cells, and hypoxic environments. In this article, the role of the extra-cellular matrix proteins and soluble mediators that acts as communicators between mesenchymal stem cells and cancer cells has been reviewed specifically for breast cancer, as it is the leading member of cancer malignancies. The comprehensive information may be beneficial in finding a new combinatorial cytotherapeutic strategy using MSCs by exploiting the cross-talk between mesenchymal stem cells and cancer cells for treating breast cancer.

The Impact of Translational Research in Breast Cancer Care: Can we Improve the Therapeutic Scenario?

2018 ◽  
Vol 18 (6) ◽  
pp. 832-836
Author(s):  
Giuseppe Buono ◽  
Francesco Schettini ◽  
Francesco Perri ◽  
Grazia Arpino ◽  
Roberto Bianco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Translational Research ◽  
Cell Biology ◽  
Cancer Biology ◽  
Hormone Receptors ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Molecular Heterogeneity ◽  
Therapeutic Implications ◽  
The Impact

Traditionally, breast cancer (BC) is divided into different subtypes defined by immunohistochemistry (IHC) according to the expression of hormone receptors and overexpression/amplification of human epidermal growth factor receptor 2 (HER2), with crucial therapeutic implications. In the last few years, the definition of different BC molecular subgroups within the IHC-defined subtypes and the identification of the important role that molecular heterogeneity can play in tumor progression and treatment resistance have inspired the search for personalized therapeutic approaches. In this scenario, translational research represents a key strategy to apply knowledge from cancer biology to the clinical setting, through the study of all the tumors “omics”, including genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Importantly, the introduction of new high-throughput technologies, such as next generation sequencing (NGS) for the study of cancer genome and transcriptome, greatly amplifies the potential and the applications of translational research in the oncology field. Moreover, the introduction of new experimental approaches, such as liquid biopsy, as well as new-concept clinical trials, such as biomarker-driven adaptive studies, may represent a turning point for BC translational research. </P><P> It is likely that translational research will have in the near future a significant impact on BC care, especially by giving us the possibility to dissect the complexity of tumor cell biology and develop new personalized treatment strategies.

scholarly journals A New Paradigm in the Relationship between Melatonin and Breast Cancer: Gut Microbiota Identified as a Potential Regulatory Agent

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3141
Author(s):  
Aurora Laborda-Illanes ◽  
Lidia Sánchez-Alcoholado ◽  
Soukaina Boutriq ◽  
Isaac Plaza-Andrades ◽  
Jesús Peralta-Linero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gut Microbiota ◽  
Bacterial Population ◽  
Kynurenine Pathway ◽  
New Paradigm ◽  
Bacterial Composition ◽  
Glucuronidase Activity ◽  
The One ◽  
The Relationship ◽  
Melatonin Production

In this review we summarize a possible connection between gut microbiota, melatonin production, and breast cancer. An imbalance in gut bacterial population composition (dysbiosis), or changes in the production of melatonin (circadian disruption) alters estrogen levels. On the one hand, this may be due to the bacterial composition of estrobolome, since bacteria with β-glucuronidase activity favour estrogens in a deconjugated state, which may ultimately lead to pathologies, including breast cancer. On the other hand, it has been shown that these changes in intestinal microbiota stimulate the kynurenine pathway, moving tryptophan away from the melatonergic pathway, thereby reducing circulating melatonin levels. Due to the fact that melatonin has antiestrogenic properties, it affects active and inactive estrogen levels. These changes increase the risk of developing breast cancer. Additionally, melatonin stimulates the differentiation of preadipocytes into adipocytes, which have low estrogen levels due to the fact that adipocytes do not express aromatase. Consequently, melatonin also reduces the risk of breast cancer. However, more studies are needed to determine the relationship between microbiota, melatonin, and breast cancer, in addition to clinical trials to confirm the sensitizing effects of melatonin to chemotherapy and radiotherapy, and its ability to ameliorate or prevent the side effects of these therapies.

scholarly journals Collagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masahiko Terajima ◽  
Yuki Taga ◽  
Becky K. Brisson ◽  
Amy C. Durham ◽  
Kotaro Sato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Mammary Carcinoma ◽  
Cancer Biology ◽  
Type I Collagen ◽  
Critical Role ◽  
Premature Death ◽  
Mammary Tissue ◽  
Type I ◽  
Cross Links

AbstractIn spite of major advances over the past several decades in diagnosis and treatment, breast cancer remains a global cause of morbidity and premature death for both human and veterinary patients. Due to multiple shared clinicopathological features, dogs provide an excellent model of human breast cancer, thus, a comparative oncology approach may advance our understanding of breast cancer biology and improve patient outcomes. Despite an increasing awareness of the critical role of fibrillar collagens in breast cancer biology, tumor-permissive collagen features are still ill-defined. Here, we characterize the molecular and morphological phenotypes of type I collagen in canine mammary gland tumors. Canine mammary carcinoma samples contained longer collagen fibers as well as a greater population of wider fibers compared to non-neoplastic and adenoma samples. Furthermore, the total number of collagen cross-links enriched in the stable hydroxylysine-aldehyde derived cross-links was significantly increased in neoplastic mammary gland samples compared to non-neoplastic mammary gland tissue. The mass spectrometric analyses of type I collagen revealed that in malignant mammary tumor samples, lysine residues, in particular those in the telopeptides, were markedly over-hydroxylated in comparison to non-neoplastic mammary tissue. The extent of glycosylation of hydroxylysine residues was comparable among the groups. Consistent with these data, expression levels of genes encoding lysyl hydroxylase 2 (LH2) and its molecular chaperone FK506-binding protein 65 were both significantly increased in neoplastic samples. These alterations likely lead to an increase in the LH2-mediated stable collagen cross-links in mammary carcinoma that may promote tumor cell metastasis in these patients.

Sign in / Sign up

Export Citation Format

Share Document