Abstract P4-04-08: EphA4-deleted microenvironment regulates cancer development of isografted 4T1 murine breast cancer cells via reduction of an IGF1 signal

It has long been established that diet and nutrition can have a significant impact on health and even help reduce the prevalence of chronic diseases. It makes sense that what we put into our bodies would have some bearing on how our bodies function. Indeed, the World Health Organization developed guidelines focusing on nutrient intake, with a view to reducing the global burden of disease related to obesity, diabetes, cardiovascular disease, several forms of cancer, osteoporosis and dental disease. One exciting area of research, that is little understood, is the potential efficacy of lunasin – a peptide found in soy, legume and some cereal grains – against certain types of cancer. Lunasin has shown potential in the prevention of cancers. It is able to do this by suppressing the proliferation and migration of cancer cells, and anti-inflammation in this tumour environment. A specific area of study within this is lunasin's ability to reduce obesity associated breast cancer development. Associate Professor Chia-Chien Hsieh, a researcher based at the Programs of Nutrition Science, School of Life Science, National Taiwan Normal University, current work is focused on the mechanism of lunasin's effect on the growth of breast cancer cells induced by obesity-associated inflammation. Her goal is to investigate the obesity-related breast cancer chemoprevention of lunasin, which might retard inflammatory responses around tumour microenvironment and even break the crosstalk of macrophages, adipocyte, and breast cancer cells. The aim being to provide potential strategies for ameliorating obesity-related ER(+) or ER(-) breast cancer development.

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HDL and LDL: Potential New Players in Breast Cancer Development

Journal of Clinical Medicine ◽

10.3390/jcm8060853 ◽

2019 ◽

Vol 8 (6) ◽

pp. 853 ◽

Cited By ~ 21

Author(s):

Lídia Cedó ◽

Srinivasa T. Reddy ◽

Eugènia Mato ◽

Francisco Blanco-Vaca ◽

Joan Carles Escolà-Gil

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Oxidative Modification ◽

Cancer Development ◽

High Density Lipoproteins ◽

Breast Cancer Development

Breast cancer is the most prevalent cancer and primary cause of cancer-related mortality in women. The identification of risk factors can improve prevention of cancer, and obesity and hypercholesterolemia represent potentially modifiable breast cancer risk factors. In the present work, we review the progress to date in research on the potential role of the main cholesterol transporters, low-density and high-density lipoproteins (LDL and HDL), on breast cancer development. Although some studies have failed to find associations between lipoproteins and breast cancer, some large clinical studies have demonstrated a direct association between LDL cholesterol levels and breast cancer risk and an inverse association between HDL cholesterol and breast cancer risk. Research in breast cancer cells and experimental mouse models of breast cancer have demonstrated an important role for cholesterol and its transporters in breast cancer development. Instead of cholesterol, the cholesterol metabolite 27-hydroxycholesterol induces the proliferation of estrogen receptor-positive breast cancer cells and facilitates metastasis. Oxidative modification of the lipoproteins and HDL glycation activate different inflammation-related pathways, thereby enhancing cell proliferation and migration and inhibiting apoptosis. Cholesterol-lowering drugs and apolipoprotein A-I mimetics have emerged as potential therapeutic agents to prevent the deleterious effects of high cholesterol in breast cancer.

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Butyl octyl phthalate interacts with estrogen receptor α in MCF‑7 breast cancer cells to promote cancer development

World Academy of Sciences Journal ◽

10.3892/wasj.2021.92 ◽

2021 ◽

Vol 3 (2) ◽

Author(s):

Madeleine Böckers ◽

Norbert Paul ◽

Thomas Efferth

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Estrogen Receptor Α ◽

Cancer Development ◽

Mcf 7

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Pan-Cancer Analysis of Molecular Characteristics and Oncogenic Role of PRMT5 in Human Cancers

10.21203/rs.3.rs-681971/v1 ◽

2021 ◽

Author(s):

He Liu ◽

Lexi Huang ◽

Kunpeng Jia ◽

Xiaohua Pan

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Molecular Mechanisms ◽

The Cancer Genome Atlas ◽

Cancer Development ◽

Nuclear Antigen ◽

Molecular Characteristics ◽

Importance Value ◽

Pan Cancer

Abstract Background Accumulating evidence supports the correlation of protein arginine methyltransferase 5 (PRMT5) and cancers development. However, the expression and prognostic values of PRMT5 in various cancers have not been clarified. Methods Here, based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, we performed a pan-cancer analysis to explore the expression profile , prognostic value landscape, relationship with tumor-infiltrating immune cells, and potential molecular mechanisms of PRMT5 in cancer development. Moreover, CCK8, wound healing and transwell assays, and western blotting analysis were conducted to evaluate how PRMT5 affects the proliferation and migration, and expression of related hallmarks in breast cancer cells. Results We found that PRMT5 was upregulated in most cancers and PRMT5 harbored distinct prognostic values across different cancer types. In addition, PRMT5 expression was negatively correlated with CD8 + T cells in tumors of cervical squamous cell carcinoma and endocervical adenocarcinoma (CSEC) and Skin Cutaneous Melanoma (SKCM), and positively correlated with the cancer-associated fibroblasts in tumors of adrenocortical carcinoma, CESC, cholangio carcinoma, liver hepatocellular carcinoma, pancreatic adenocarcinoma, and SKCM-Primary. Moreover, the enrichment analysis identified that PRMT5 mechanistically regulated cancers development by acting on DNA and RNA metabolism, and stress response related pathways. By further gene silencing experiment, we confirmed tha t PRMT5 knockdown reduced the proliferative and migrative capacities, as well as the expression of PCNA (proliferating cell nuclear antigen), p21 and HMGB1 (high mobility group box 1 protein) in breast cancer cells. Conclusion Collectively, our pan-cancer study highlighted the importance value of PRMT5 in cancer development and prognosis, and pharmacologic targeting at PRMT5 may provide a novel approach for the treatment of cancers.

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Antitumoral Potential of Lansbermin-I, a Novel Disintegrin from Porthidium lansbergii lansbergii Venom on Breast Cancer Cells

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190806151401 ◽

2019 ◽

Vol 19 (22) ◽

pp. 2069-2078 ◽

Cited By ~ 4

Author(s):

Leonel Montealegre-Sánchez ◽

Sarah N.C. Gimenes ◽

Daiana S. Lopes ◽

Samuel C. Teixeira ◽

Luis Solano-Redondo ◽

...

Keyword(s):

Breast Cancer ◽

Platelet Aggregation ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Platelet Rich Plasma ◽

High Specificity ◽

Cancer Development ◽

Mcf7 Cells ◽

Huvec Cells

Background: Disintegrins from snake venoms bind with high specificity cell surface integrins, which are important pharmacological targets associated with cancer development and progression. Objective: In this study, we isolated a disintegrin from the Porthidium lansbergii lansbergii venom and evaluated its antitumoral effects on breast cancer cells. Methods: The isolation of the disintegrin was performed on RP-HPLC and the inhibition of platelet aggregation was evaluated on human platelet-rich plasma. The inhibition of cell adhesion was also evaluated in vitro on cultures of cell lines by the MTT method as well as the inhibition of breast cancer cell migration by the wound healing assay. The binding of the disintegrin to integrin subunits was verified by flow cytometry and confocal microscopy. Finally, inhibition of angiogenesis was assessed in vitro on HUVEC cells and the concentration of VEGF was measured in the cellular supernatants. Results: The disintegrin, named Lansbermin-I, is a low molecular weight protein (< 10 kDa) that includes an RGD on its sequence identified previously. Lansbermin-I showed potent inhibition of ADP and collagen-induced platelet aggregation on human plasma and also displayed inhibitory effects on the adhesion and migration of breast cancer MCF7 and MDA-MB 231cell lines, without affecting nontumorigenic breast MCF-10A and lung BEAS cells. Additionally, Lansbermin-I prevented MCF7 cells to adhere to fibronectin and collagen, and also inhibited in vitro angiogenesis on human endothelial HUVEC cells. Conclusion: Our results display the first report on the antitumor and anti-metastatic effects of an RGDdisintegrin isolated from a Porthidium snake venom by possibly interfering with α2 and/or β1-containing integrins. Thus, Lansbermin-I could be an attractive model to elucidate the role of disintegrins against breast cancer development.

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Featured Article: Downregulation of transgelin blocks interleukin-8 utilization and suppresses vasculogenic mimicry in breast cancer cells

Experimental Biology and Medicine ◽

10.1177/1535370216685435 ◽

2017 ◽

Vol 242 (6) ◽

pp. 573-583 ◽

Cited By ~ 14

Author(s):

Anastasia R Aikins ◽

MiJung Kim ◽

Bernardo Raymundo ◽

Chan-Wha Kim

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Future Development ◽

Breast Cancer Cells ◽

Vasculogenic Mimicry ◽

Tube Formation ◽

Cancer Development ◽

Actin Binding ◽

Actin Binding Protein ◽

Multiple Stages

Vasculogenic mimicry (VM) is a non-classical mechanism recently described in many tumors, whereby cancer cells, rather than endothelial cells, form blood vessels. Transgelin is an actin-binding protein that has been implicated in multiple stages of cancer development. In this study, we investigated the role of transgelin in VM and assessed its effect on the expression of endothelial and angiogenesis-related genes during VM in MDA-MB-231 breast cancer cells. We confirmed the ability of MDA-MB-231 cells to undergo VM through a tube formation assay. Flow cytometry analysis revealed an increase in the expression of the endothelial-related markers VE-cadherin and CD34 in cells that underwent VM, compared with those growing in a monolayer, which was confirmed by immunocytochemistry. We employed siRNA to silence transgelin, and knockdown efficiency was determined by western blot analyses. Downregulation of transgelin suppressed cell proliferation and tube formation, but increased IL-8 levels in Matrigel cultures. RT-PCR analyses revealed that the expression of IL-8, VE-cadherin, and CD34 was unaffected by transgelin knockdown, indicating that increased IL-8 expression was not due to enhanced transcriptional activity. More importantly, the inhibition of IL-8/CXCR2 signaling also resulted in suppression of VM with increased IL-8 levels, confirming that increased IL-8 levels after transgelin knockdown was due to inhibition of IL-8 uptake. Our findings indicate that transgelin regulates VM by enhancing IL uptake. These observations are relevant to the future development of efficient antivascular agents. Impact statement Vasculogenic mimicry (VM) is an angiogenic-independent mechanism of blood vessel formation whereby aggressive tumor cells undergo formation of capillary-like structures. Thus, interventions aimed at angiogenesis might not target the entire tumor vasculature. A more holistic approach is therefore needed in the development of improved antivascular agents. Transgelin, an actin-binding protein, has been associated with multiple stages of cancer development such as proliferation, migration and invasion, but little is known about its role in vasculogenic mimicry. We present here, an additional mechanism by which transgelin promotes malignancy by way of its association with the occurrence of VM. Although transgelin knockdown did not affect the transcript levels of most of the angiogenesis-related genes in this study, it was associated with the inhibition of the uptake of IL-8, accompanied by suppressed VM, indicating that transgelin is required for VM. These observations are relevant to the future development of efficient antivascular agents.

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Inhibiting mir-29 and targeting ADAM12: lidocaine inhibits breast cancer development

10.21203/rs.3.rs-29016/v1 ◽

2020 ◽

Author(s):

Gui Feng ◽

Fei He

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Apoptosis ◽

Breast Cancer Cells ◽

Cell Counting ◽

Cancer Development ◽

Luciferase Reporter ◽

Cancer Cell Proliferation

Abstract Breast cancer is the most common cancers among women in the world. For hundreds of years, researchers are devoted for developing new strategy against cancer. As a rapid and effective local anesthetic, lidocaine is reported having multiple-physiological functions in clinic treatment, such as anti-cancer and anti-inflammatory activity. Besides, the microRNAs (miRNAs) have been demonstrated to be involved in the cancer development, and the miRNA-29 family is abnormally expressed in a variety of cancers, which could not only regulate the cancer cell proliferation, migration and invasion, but also promote cancer cell apoptosis by binding to target proteins. However, the protective effect of lidocaine on breast cancer cells and the mechanism was still unclear. In the present study, the relative expression level of the miRNA-29 in cancer cells and tissues was measured with quantitative RT-PCR. Bioinformatic analysis was performed to predict the potential target of the miRNA-29 in breast cancer cells, and the luciferase reporter assay was employed to validate the direct binding of the target protein and the miRNA-29 in breast cancer cells. Cell Counting Kit-8 (CCK-8) and the Cell Apoptosis Assay Kit were utilized to analyze the cancer cell proliferation and apoptosis after lidocaine treatment.

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Nicotine Synergizes with High-Fat Diet to Induce an Anti-Inflammatory Microenvironment to Promote Breast Tumor Growth

Mediators of Inflammation ◽

10.1155/2020/5239419 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Thalia Jimenez ◽

Theodore Friedman ◽

Jaydutt Vadgama ◽

Vineeta Singh ◽

Alexandria Tucker ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Breast Tumor ◽

High Fat Diet ◽

Breast Cancer Cells ◽

Cancer Development ◽

High Fat ◽

Breast Cancer Development ◽

Anti Inflammatory

Breast cancer results from a complex interplay of genetics and environment that alters immune and inflammatory systems to promote tumorigenesis. Obesity and cigarette smoking are well-known risk factors associated breast cancer development. Nicotine known to decrease inflammatory signals also modulates immune responses that favor breast cancer development. However, the mechanisms by which nicotine and obesity contribute to breast cancer remain poorly understood. In this study, we examined potential mechanisms by which nicotine (NIC) and high-fat diet (HFD) promote growth of HCC70 and HCC1806 xenografts from African American (AA) triple negative (TN) breast cancer cells. Immunodeficient mice fed on HFD and treated with NIC generated larger HCC70 and HCC1806 tumors when compared to NIC or HFD alone. Increased xenograft growth in the presence of NIC and HFD was accompanied by higher levels of tissue-resident macrophage markers and anti-inflammatory cytokines including IL4, IL13, and IL10. We further validated the involvement of these players by in vitro and ex vivo experiments. We found a proinflammatory milieu with increased expression of IL6 and IL12 in xenografts with HFD. In addition, nicotine or nicotine plus HFD increased a subset of mammary cancer stem cells (MCSCs) and key adipose browning markers CD137 and TMEM26. Interestingly, there was upregulation of stress-induced pp38 MAPK and pERK1/2 in xenografts exposed to HFD alone or nicotine plus HFD. Scratch-wound assay showed marked reduction in proliferation/migration of nicotine and palmitate-treated breast cancer cells with mecamylamine (MEC), a nicotine acetylcholine receptor (nAchR) antagonist. Furthermore, xenograft development in immune-deficient mice, fed HFD plus nicotine, was reduced upon cotreatment with MEC and SB 203580, a pp38MAPK inhibitor. Our study demonstrates the presence of nicotine and HFD in facilitating an anti-inflammatory tumor microenvironment that influences breast tumor growth. This study also shows potential efficacy of combination therapy in obese breast cancer patients who smoke.

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