scholarly journals Breast Cancer Cells Interact with Osteoblasts to Support Osteoclast Formation1

Endocrinology ◽  
1999 ◽  
Vol 140 (10) ◽  
pp. 4451-4458 ◽  
Author(s):  
Rachel J. Thomas ◽  
Theresa A. Guise ◽  
Juan Juan Yin ◽  
Jan Elliott ◽  
Nicole J. Horwood ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Messenger Rna ◽  
Cancer Metastasis ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Breast Cancer Cell Lines ◽  
Mrna Levels ◽  
Breast Cancers ◽  
Receptor Activator ◽  
Mcf 7

Abstract Breast cancers commonly cause osteolytic metastases in bone, a process that is dependent upon osteoclast-mediated bone resorption. Recently the osteoclast differentiation factor (ODF), better termed RANKL (receptor activator of NF-κB ligand), expressed by osteoblasts has been cloned as well as its cognate signaling receptor, receptor activator of NFκB (RANK), and a secreted decoy receptor osteoprotegerin (OPG) that limits RANKL’s biological action. We determined that the breast cancer cell lines MDA-MB-231, MCF-7, and T47D as well as primary breast cancers do not express RANKL but express OPG and RANK. MCF-7, MDA-MB-231, and T47D cells did not act as surrogate osteoblasts to support osteoclast formation in coculture experiments, a result consistent with the fact that they do not express RANKL. When MCF-7 cells overexpressing PTH-related protein (PTHrP) were added to cocultures of murine osteoblasts and hematopoietic cells, osteoclast formation resulted without the addition of any osteotropic agents; cocultures with MCF-7 or MCF-7 cells transfected with pcDNAIneo required exogenous agents for osteoclast formation. When MCF-7 cells overexpressing PTHrP were cultured with murine osteoblasts, osteoblastic RANKL messenger RNA (mRNA) levels were enhanced and osteoblastic OPG mRNA levels diminished; MCF-7 parental cells had no effect on RANKL or OPG mRNA levels when cultured with osteoblastic cells. Using a murine model of breast cancer metastasis to bone, we established that MCF-7 cells that overexpress PTHrP caused significantly more bone metastases, which were associated with increased osteoclast formation, elevated plasma PTHrP concentrations and hypercalcaemia compared with parental or empty vector controls.

scholarly journals Increased 12-Lipoxygenase Expression in Breast Cancer Tissues and Cells. Regulation by Epidermal Growth Factor1

1997 ◽  
Vol 82 (6) ◽  
pp. 1790-1798 ◽  
Author(s):  
Rama Natarajan ◽  
Robert Esworthy ◽  
Wei Bai ◽  
Jia-Li Gu ◽  
Sharon Wilczynski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Breast Epithelial Cell ◽  
Mrna Levels ◽  
Epidermal Growth ◽  
Mcf 7

Abstract The interaction of growth factors, such as epidermal growth factor (EGF) with their receptors, on breast cancer cells can lead to the hydrolysis of phospholipids and release of fatty acids, such as arachidonic acid, which can be further metabolized by the lipoxygenase (LO) pathway. Several LO products have been shown to stimulate oncogenes and have mitogenic and chemotactic effects. In this study, we have evaluated the regulation of 12-LO activity and expression in breast cancer cells and tissues. Leukocyte-type 12-LO messenger RNA (mRNA) expression was studied by a specific RT-PCR method in matched, normal, uninvolved and cancer-involved breast tissue RNA samples from six patients. In each of these six patients, the cancer-involved section showed a much higher level of 12-LO mRNA than the corresponding normal section. 12-LO mRNA levels also were greater in two breast cancer cell lines, MCF-7 and COH-BR1, compared with the nontumorigenic breast epithelial cell line, MCF-10F. The growth of the MCF-7 cells was significantly inhibited by two specific LO blockers but not by a cyclooxygenase blocker. Treatment of serum-starved MCF-7 cells with EGF for 4 h led to a dose-dependent increase in the formation of the 12-LO product, 12-hydroxyeicosatetraenoic acid. EGF treatment also increased the levels of the leukocyte-type 12-LO protein expression at 24 h. These results suggest that activation of the 12-LO pathway may play a key role in basal and EGF-induced breast cancer cell growth.

scholarly journals One-Step 18F-Labeling of Estradiol Derivative for PET Imaging of Breast Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Hongbo Huang ◽  
Ke Li ◽  
Gaochao Lv ◽  
Guiqing Liu ◽  
Xueyu Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pet Imaging ◽  
Cell Uptake ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Isotope Exchange Reaction ◽  
Er Positive ◽  
One Step ◽  
Mcf 7

Positron emission tomography (PET) imaging is a useful method to evaluate in situ estrogen receptor (ER) status for the early diagnosis of breast cancer and optimization of the appropriate treatment strategy. The 18F-labeled estradiol derivative has been successfully used to clinically assess the ER level of breast cancer. In order to simplify the radiosynthesis process, one-step 18F-19F isotope exchange reaction was employed for the 18F-fluorination of the tracer of [18F]AmBF3-TEG-ES. The radiotracer was obtained with the radiochemical yield (RCY) of ~61% and the radiochemical purity (RCP) of >98% within 40 min. Cell uptake and blocking assays indicated that the tracer could selectively accumulate in the ER-positive human breast cancer cell lines MCF-7 and T47D. In vivo PET imaging on the MCF-7 tumor-bearing mice showed relatively high tumor uptake (1.4~2.3 %D/g) and tumor/muscle uptake ratio (4~6). These results indicated that the tracer is a promising PET imaging agent for ER-positive breast cancers.

scholarly journals Dihydroartemisinin-loaded Magnetic Nanoparticles for Enhanced Chemodynamic Therapy

2019 ◽  
Author(s):  
Shengdi Guo ◽  
Xianxian Yao ◽  
Qin Jiang ◽  
Kuang Wang ◽  
Yuanying Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Magnetic Nanoparticles ◽  
Cancer Cells ◽  
Therapeutic Effect ◽  
Breast Cancer Cells ◽  
Inhibitory Effect ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Ferrous Ions ◽  
Mcf 7

AbstractRecently, chemodynamic therapy (CDT) has represented a new approach for cancer treatment with low toxicity and side effects. Nonetheless, it has been a challenge to improve the therapeutic effect through increasing the amount of reactive oxygen species (ROS). Herein, we increased the amount of ROS agents in the Fenton-like reaction by loading dihydroartemisinin (DHA) which was an artemisinin (ART) derivative containing peroxide groups, into magnetic nanoparticles (MNP), thereby improving the therapeutic effect of CDT. Blank MNP were almost non-cytotoxic, whereas three MNP loading ART-based drugs, MNP-ART, MNP-DHA, and MNP-artesunate (MNP-AS), all showed significant killing effect on breast cancer cells (MCF-7 cells), in which MNP-DHA were the most potent. What’s more, the MNP-DHA showed high toxicity to drug-resistant breast cancer cells (MCF-7/ADR cells), demonstrating its ability to overcome multidrug resistance (MDR). The study revealed that MNP could produce ferrous ions under the acidic condition of tumor microenvironment, which catalyzed DHA to produce large amounts of ROS, leading to cell death. Further experiments also showed that the MNP-DHA had significant inhibitory effect on another two aggressive breast cancer cell lines (MDA-MB-231 and MDA-MB-453 cells), which indicated that the great potential of MNP-DHA for the treatment of intractable breast cancers.

scholarly journals The Potential Utility of Curcumin in the Treatment of HER-2-Overexpressed Breast Cancer: AnIn VitroandIn VivoComparison Study with Herceptin

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Hung-Wen Lai ◽  
Su-Yu Chien ◽  
Shou-Jen Kuo ◽  
Ling-Ming Tseng ◽  
Hui-Yi Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Cell Growth ◽  
Xenograft Model ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Her 2 ◽  
Mcf 7

HER-2 is an important oncoprotein overexpressed in about 15–25% of breast cancers. We hypothesized that the ability of curcumin to downregulate HER-2 oncoprotein and inhibit the signal transduction pathway of PI3K/Akt, MAPK, and NF-κB activation may be important in the treatment of HER-2-overexpressed breast cancer. To examine the effect of curcumin on breast cancer cells, MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr (a herceptin resistant strain from SK-BR-3) cells were used forin vitroanalysis. Thein vivoeffect of curcumin on HER-2-overexpressed breast cancer was investigated with the HER-2-overexpressed BT-474 xenograft model. Cell growth, cell cycle change, the antimobility effect, signal transduction, and xenograft volume analysis between groups treated with herceptin and/or curcumin were tested. Curcumin decreased the cell growth of various breast cancer cell lines (MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr). In Western blot analysis, the phosphorylation of Akt, MAPK, and expression of NF-κB were reduced in BT-474 cells, but not in SK-BR-3-hr cells, after treatment with herceptin. When treated with curcumin, the HER-2 oncoprotein, phosphorylation of Akt, MAPK and expression of NF-κB were decreased in both BT-474 and SK-BR-3-hr cells. In the BT-474 xenograft model, though not as much as herceptin, curcumin did effectively decrease the tumor size. The combination of curcumin with herceptin was not better than herceptin alone; however, the combination of taxol and curcumin had an antitumor effect comparable with taxol and herceptin. The results suggested that curcumin has potential as a treatment for HER-2-overexpressed breast cancer.

scholarly journals In Vitro Modeling of Reoxygenation Effects on mRNA and Protein Levels in Hypoxic Tumor Cells upon Entry into the Bloodstream

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1316 ◽  
Author(s):  
Kai Bartkowiak ◽  
Claudia Koch ◽  
Sebastian Gärtner ◽  
Antje Andreas ◽  
Tobias M Gorges ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Bone Marrow Cells ◽  
Breast Cancer Cell Lines ◽  
Mrna Levels ◽  
Protein Levels ◽  
Biopsy Methods ◽  
Independent Translation ◽  
Mcf 7

Background: Solid epithelial tumors like breast cancer are the most frequent malignancy in women. Circulating tumor cells (CTCs) are frequently released from hypoxic areas into the blood, where CTCs face elevated oxygen concentrations. This reoxygenation might challenge the use of CTCs for liquid biopsy. Methods: We modeled this situation in vitro using the breast cancer cell lines—MCF-7, MDA-MB-468, MDA-MB-231—and the cell line BC-M1 established from DTCs in the bone marrow. Cells were cultured under hypoxia, followed by a reoxygenation pulse for 4 h, reflecting the circulation time of CTCs. Analyzed were gene products like EGFR, ErbB-2, EpCAM, PD-L1 on mRNA and protein level. Results: mRNAs of erbb2 or pdl1 and protein levels of PD-L1 displayed significant changes, whereas ErbB-2 protein levels remained constant. The strongest discrepancy between protein and mRNA levels under hypoxia was observed for EGFR, supporting the idea of cap-independent translation of egfr mRNA. Analyses of the phosphorylation of AKT, Erk 1/2, and Stat3 revealed strong alterations after reoxygenation. Conclusions: CTCs reaching secondary sites faster than reoxygenation could alter the mRNA and protein levels in the cells. CTC and DTC with high PD-L1 levels might become quiescent under hypoxia but were easily reactivated by reoxygenation.

scholarly journals Malic enzyme 1 may be a novel target of breast cancer metastasis

2019 ◽  
Author(s):  
Chang Liu ◽  
Shuchen Lin ◽  
Yannan Zhao ◽  
Jun Cao ◽  
Zhonghua Tao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Malic Enzyme ◽  
Prognostic Value ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Cell Lines ◽  
Public Database ◽  
The Public ◽  
Mcf 7

Abstract Background Malic enzyme 1 (ME1) catalyzes malate to pyruvate and thus promotes glycolysis, playing a part in the Warburg effect. It also has a potential role in tumor progression, but its function in breast cancer remains to be fully clarified. This work aimed to investigate the prognostic value of ME1 and its possible mechanism in breast cancer.Methods We evaluated ME1 expression in 220 early breast cancer patients with tissue microarray-based immunohistochemistry and explored the relationships between ME1 expression and clinicopathological features. Survival analyses were further performed to determine its prognostic value. The public database was used to confirm tissue microarray results. Moreover, we profiled ME1 expression in breast cancer cell lines via western blotting, and then assessed it in cell viability and motility via Cell counting kit-8 (CCK-8), colony formation, transwell migration and invasion assays. Reactive oxygen species (ROS) was detected by dihydroethidium (DHE) and 2’,7’-Dichlorodihydrofluorescein diacetate (DCFH-DA).Results In breast cancer tissues, high ME1 expression was significantly associated with larger tumor size, more lymph node metastasis and more extensive lymph-vascular invasion. Survival analysis showed high ME1 expression was significantly correlated with worse recurrence free survival (RFS). Multivariate analysis further identified high ME1 expression as an independent prognostic factor for RFS, which was confirmed by mRNA results in the public database. In vitro , human epidermal growth factor receptor-2 positive and triple negative breast cancer cell lines showed higher expression of ME1, while Luminal cell lines showed lower expression of ME1. Upregulation of ME1 by transfecting MCF-7 cells with virus vector remarkably enhanced viability and motility, epithelial-mesenchymal transition (EMT), and decreased ROS levels, whereas knockdown of this gene in MDA-MB-468 cells produced totally opposite effects as expected. More important, when pretreated with hydrogen peroxide, an oxidizing agent, MCF-7 cells overexpressing ME1 lost its motility, whereas MDA-MB-468 cells with knock-down of ME1 restored its motility when pretreated with N-acetyl cysteine, an antioxidant.Conclusions To our knowledge, these clinical and experiment work first suggested that ME1 may be a potential therapeutic target for breast cancer metastasis, and its biological effect is mainly controlled by manipulating ROS.

scholarly journals WNK1 Enhances Migration and Invasion in Breast Cancer Models

2021 ◽  
Author(s):  
Ankita B. Jaykumar ◽  
Jiung Jung ◽  
Pravat Parida ◽  
Tuyen T. Dang ◽  
Magdalena Grzemska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Collagen Matrices ◽  
Cancer Models ◽  
Protein Components

AbstractMetastasis is the major cause of mortality in breast cancer patients. Many signaling pathways have been linked to cancer invasiveness, but blockade of few protein components has succeeded in reducing metastasis. Thus, identification of proteins contributing to invasion that are manipulable by small molecules may be valuable in inhibiting spread of the disease. The protein kinase WNK1 (with no lysine (K) 1) has been suggested to induce migration of cells representing a range of cancer types. Analyses of mouse models and patient data have implicated WNK1 as one of a handful of genes uniquely linked to invasive breast cancer. Here we present evidence that inhibition of WNK1 slows breast cancer metastasis. We show that depletion or inhibition of WNK1 reduces migration of several breast cancer cell lines in wound healing assays and decreases invasion in collagen matrices. Furthermore, WNK1 depletion suppresses expression of AXL, a tyrosine kinase implicated in metastasis. Finally, we demonstrate that WNK inhibition in mice attenuates tumor progression and metastatic burden. These data showing reduced migration, invasion, and metastasis upon WNK1 depletion in multiple breast cancer models suggest that WNK1 contributes to the metastatic phenotype and that WNK1 inhibition may offer a therapeutic avenue for attenuating progression of invasive breast cancers.

Purinergic mechanisms in breast cancer metastasis.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 229-229
Author(s):  
I. L. Buxton
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Receptor Antagonist ◽  
Cancer Metastasis ◽  
Purinergic Receptor ◽  
Receptor Activation ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Human Endothelial Cells

229 Background: Breast cancers survive in patients in a dormant state only to grow as metastatic disease in the future. Surgery to remove the primary tumor often terminates dormancy resulting in accelerated relapses. Many breast cancer deaths might be averted if we understand the cellular mechanisms underlying escape from dormancy. We have proposed that extracellular nucleotide signaling constitutes a pathological axis from the transformed tumor cell to the endothelium in the service of intravasation, dissemination, extravasation and angiogenesis. We demonstrate a role for the dinucleotide kinase NM23/NDPK in the generation of signals that stimulate angiogenesis and escape from latency. Methods: We have employed protein purification and identification by Western blot, tubulogenesis, migration and proliferation assays in human endothelial cells, signaling assays of receptor activation, nucleotide and receptor transactivation/phosphorylation assays and tumor growth and metastasis imaging in immunocompromized mice (SCID) to establish a role of r nucleotides in breast cancer metastasis. Results: A panel of breast cancer cell lines, but not normal breast cells, shed/secrete large amounts of NM23 that is active as an ADP transphosphorylase. NM23 stimulates tubulogenesis, proliferation and migration in cultures of human endothelial cells in a manner blocked by purinergic receptor antagonist, inhibitors of the nucleoside diphosphate kinase activity of NM23, or by VEGFR2 antagonists. In SCID mice carrying MDA-MB-231 luciferase over-expressing breast cancers, NM23 appears in the blood early in tumorigenesis. Treatment with the P2Y1 receptor antagonist MRS2179, or the NM23 antagonist ellagic acid slows the growth of primary breast tumors and prevents metastatic tumor formation. Conclusions: NM23 secretion leading to nucleotide generation activates endothelial P2Y1 receptors resulting in transactivation of VEGFR2 and angiogenesis in support of metastasis. Identification of Nm23 as a marker of early of breast cancer development and blockade of the extracellular actions of NM23 offer a new approach to breast cancer detection and treatment.

scholarly journals Expression of somatostatin receptors subtypes (1-5) mRNA in MCF7 and MDA-MB231 breast cancer human cell lines

2020 ◽  
Author(s):  
ALKHANSA MAHMOUD ◽  
Maria Teresa Mancuso ◽  
Barbara Tanno ◽  
Zuki Abu Bakar ◽  
Hazilawati Hamzah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cell Lines ◽  
Quantitative Polymerase Chain Reaction ◽  
Somatostatin Receptors ◽  
Breast Cancer Cell Lines ◽  
Mrna Levels ◽  
Mcf7 Cells ◽  
Polymerase Chain ◽  
Mcf 7

Abstract Background: breast cancer is one of most common types of cancer and heterogeneous disease. Somatostatain receptors (SSTR1-5) are expressed in breast cancer cells. MCF7 and MDA-MB231 cell lines used to evaluate the expression of somatostatin receptors (SSTRs 1 - 5). Methods: The detection of mRNA expression levels of SSTRs in MCF7 and MDA-MB231 was performed using quantitative- polymerase chain reaction (qPCR). Results: All SSTRs 1 - 5 were expressed in both cells lines. The SSTR 1, 2, 3 and 4 mRNA levels were significantly higher in MDA-MB-231 in relation to MCF-7. The expression of SSTR 4 and 5 mRNA was highest in MDA-MB231 and MCF-7 cell lines respectively, however, SSTR3 mRNA was least expressed in both cell lines. Conclusion: All SSTRs were expressed in both MDA-MB231 and MCF7 cells. However, the levels of expression differ between both cell lines. Keywords: Breast cancer. Cell lines .Somatostatin receptors. mRNA expression

Cytotoxic activity and anti-cancer potential of Ontario grown onion extracts against breast cancer cell lines

2018 ◽  
Vol 8 (3) ◽  
pp. 159 ◽  
Author(s):  
Meghan Fragis ◽  
Abdulmonem I. Murayyan ◽  
Suresh Neethirajan
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Cancer Line ◽  
Mcf 7

Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity

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