The Mechanism of Lunasin's Effect on the Growth of Breast Cancer Cells Induced by Obesity-induced Inflammation

Impact ◽  
2020 ◽  
Vol 2020 (7) ◽  
pp. 16-18
Author(s):  
Chia-Chien Hsieh
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Inflammatory Responses ◽  
Specific Area ◽  
Tumour Microenvironment ◽  
Associate Professor ◽  
World Health ◽  
Cancer Development ◽  
Breast Cancer Development

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.

scholarly journals HDL and LDL: Potential New Players in Breast Cancer Development

2019 ◽  
Vol 8 (6) ◽  
pp. 853 ◽  
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.

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

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.

scholarly journals Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jones Gyamfi ◽  
Joo Hye Yeo ◽  
Doru Kwon ◽  
Byung Soh Min ◽  
Yoon Jin Cha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumour Microenvironment ◽  
Metabolic Reprogramming ◽  
De Novo Lipogenesis ◽  
Mesenchymal Transition ◽  
Genetic Ablation ◽  
Cd36 Expression

AbstractAdipocytes influence breast cancer behaviour via fatty acid release into the tumour microenvironment. Co-culturing human adipocytes and breast cancer cells increased CD36 expression, with fatty acid import into breast cancer cells. Genetic ablation of CD36 attenuates adipocyte-induced epithelial-mesenchymal transition (EMT) and stemness. We show a feedforward loop between CD36 and STAT3; where CD36 activates STAT3 signalling and STAT3 binds to the CD36 promoter, regulating its expression. CD36 expression results in metabolic reprogramming, with a shift towards fatty acid oxidation. CD36 inhibition induces de novo lipogenesis in breast cancer cells. Increased CD36 expression occurs with increased FABP4 expression. We showed that CD36 directly interacts with FABP4 to regulate fatty acid import, transport, and metabolism. CD36 and FABP4 inhibition induces apoptosis in tumour cells. These results indicate that CD36 mediates fatty acid import from adipocytes into cancer cells and activates signalling pathways that drive tumour progression. Targeting CD36 may have a potential for therapy, which will target the tumour microenvironment.

scholarly journals Mesenchymal stromal cell activation by breast cancer secretomes in bioengineered 3D microenvironments

2019 ◽  
Vol 2 (3) ◽  
pp. e201900304 ◽  
Author(s):  
Ulrich Blache ◽  
Edward R Horton ◽  
Tian Xia ◽  
Erwin M Schoof ◽  
Lene H Blicher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Breast Cancer Cells ◽  
Cell Activation ◽  
Tumour Microenvironment ◽  
Paracrine Signalling ◽  
Organ Specific ◽  
Mcf 7

Mesenchymal stromal cells (MSCs) are key contributors of the tumour microenvironment and are known to promote cancer progression through reciprocal communication with cancer cells, but how they become activated is not fully understood. Here, we investigate how breast cancer cells from different stages of the metastatic cascade convert MSCs into tumour-associated MSCs (TA-MSCs) using unbiased, global approaches. Using mass spectrometry, we compared the secretomes of MCF-7 cells, invasive MDA-MB-231 cells, and sublines isolated from bone, lung, and brain metastases and identified ECM and exosome components associated with invasion and organ-specific metastasis. Next, we used synthetic hydrogels to investigate how these different secretomes activate MSCs in bioengineered 3D microenvironments. Using kinase activity profiling and RNA sequencing, we found that only MDA-MB-231 breast cancer secretomes convert MSCs into TA-MSCs, resulting in an immunomodulatory phenotype that was particularly prominent in response to bone-tropic cancer cells. We have investigated paracrine signalling from breast cancer cells to TA-MSCs in 3D, which may highlight new potential targets for anticancer therapy approaches aimed at targeting tumour stroma.

scholarly journals Prolactin does not delay early tumour formation of breast cancer cells, but in combination with DNA damage can trigger an anti-tumour immune response

2020 ◽  
Author(s):  
Ödül Karayazi Atici ◽  
Carrie S. Shemanko
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumour Microenvironment ◽  
Janus Kinase ◽  
Tumour Formation ◽  
Tumour Initiation ◽  
Asialo Gm1

ABSTRACTThere are conflicting reports of the role of prolactin in breast cancer, and its role within the context of the tumour microenvironment is not well understood. In our previous study, we demonstrated a cross-talk between the ataxia telangiectasia-mutated (ATM) DNA damage response pathway and the PRL-Janus-kinase-2 (JAK2)-signal transducer and activator of transcription-5 (STAT5)-heat shock protein-90 (HSP90) pathway. In order to investigate the role of PRL in tumour initiation and the effect of DNA damage in vivo, we used a model of breast cancer initiation that assesses the ability of breast cancer cells to initiate orthotopic xenograft tumour formation after DNA damage. Breast cancer cells engineered to secrete human PRL or the control cells, were treated with the DNA damaging agent doxorubicin or vehicle and injected into mammary fat pad of immune deficient SCID mice. PRL secretion from human breast cancer cells did not change the tumour latency compared to controls, although combined doxorubicin and PRL treatment increased tumour latency. Injection of a natural killer (NK) cell-depleting antibody, anti-asialo GM1, resulted in faster tumour formation only in the PRL-secreting breast cancer cells that were pre-treated with doxorubicin, and not PRL-only or empty vector controls. These results may shed light on the conflicting reports of PRL in breast cancer, and demonstrate that at least within the context of breast cancer cell DNA damage, that PRL exposure in the tumour microenvironment does not delay tumour initiation, but PRL together with DNA damage of breast cancer cells results in reduced tumour volume over time due to asialo-GM1-positive immune cells.

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

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.

scholarly journals Mitochondrial Flexibility of Breast Cancers: A Growth Advantage and a Therapeutic Opportunity

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 401 ◽  
Author(s):  
Angelica Avagliano ◽  
Maria Rosaria Ruocco ◽  
Federica Aliotta ◽  
Immacolata Belviso ◽  
Antonello Accurso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumour Microenvironment ◽  
Metabolic Reprogramming ◽  
Cancer Tissue ◽  
Breast Cancers ◽  
Tissue Properties ◽  
Metabolic Plasticity ◽  
Mitochondrial Alterations

Breast cancers are very heterogeneous tissues with several cell types and metabolic pathways together sustaining the initiation and progression of disease and contributing to evasion from cancer therapies. Furthermore, breast cancer cells have an impressive metabolic plasticity that is regulated by the heterogeneous tumour microenvironment through bidirectional interactions. The structure and accessibility of nutrients within this unstable microenvironment influence the metabolism of cancer cells that shift between glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) to produce adenosine triphosphate (ATP). In this scenario, the mitochondrial energetic pathways of cancer cells can be reprogrammed to modulate breast cancer’s progression and aggressiveness. Moreover, mitochondrial alterations can lead to crosstalk between the mitochondria and the nucleus, and subsequently affect cancer tissue properties. This article reviewed the metabolic plasticity of breast cancer cells, focussing mainly on breast cancer mitochondrial metabolic reprogramming and the mitochondrial alterations influencing nuclear pathways. Finally, the therapeutic strategies targeting molecules and pathways regulating cancer mitochondrial alterations are highlighted.

Sign in / Sign up

Export Citation Format

Share Document