scholarly journals Interface between breast cancer cells and the tumor microenvironment using platelet-rich plasma to promote tumor angiogenesis - influence of platelets and fibrin bundles on the behavior of breast tumor cells

Oncotarget ◽  
2017 ◽  
Vol 8 (10) ◽  
pp. 16851-16874 ◽  
Author(s):  
Sheila Siqueira Andrade ◽  
Joana Tomomi Sumikawa ◽  
Eloísa Dognani Castro ◽  
Fabricio Pereira Batista ◽  
Edgar Paredes-Gamero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Tumor Angiogenesis ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Platelet Rich Plasma ◽  
Breast Tumor Cells ◽  
Promote Tumor Angiogenesis

Patterns of Cell Death Induced by Thiohydantoins in Human MCF-7 Breast Cancer Cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Tatiane Renata Fagundes ◽  
Bruna Bortoleti ◽  
Priscila Camargo ◽  
Vírgínia Concato ◽  
Fernanda Tomiotto-Pellissier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Cell Volume ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Breast Tumor Cells ◽  
Mcf 7

Background: Conventional therapies for breast cancer is still a challenge due to use of cytotoxic drugs not highly effective with major adverse effects. Thiohydantoins, are biologically active heterocyclic compounds reported by several biological activities, including anticarcinogenic properties, i.e., this work aimed to assess the use of thiohydantoin as a potential antitumor agent against MCF-7 breast cancer cells. Methods: MTT and neutral red assays were used to assess the possible cytotoxic activity of compounds against MCF-7 cells. Cell volume measurement and analysis were performed by flow cytometry, fluorescence analysis was carried out to determine patterns of cell death induced by thiohydantoins. Results: The treatment with micromolar doses of thiohydantoins promoted a decrease in the viability of MCF-7 breast tumor cells. Also were observed the increase in ROS and NO production, reduction in cell volume, loss of membrane integrity, mitochondrial depolarization, and increased fluorescence for annexin V and caspase-3. These findings indicate cell death by apoptosis and increased formation of autophagic vacuoles and stopping the cell cycle in the G1/ G0 phase. Conclusions: Our results indicate that thiohydantoins are cytotoxic to breast tumor cells, and this effect is linked to the increase in ROS production. This phenomenon changes tumorigenic pathways, that lead to a halt of the cell cycle in G1/G0, an important checkpoint for DNA errors, which may have altered the process by which cells produce energy, causing a decrease in mitochondrial viability and thus leading to the apoptotic process. Furthermore, the results indicate increased autophagy, a vital process linked to a decrease in lysosomal viability and considered as a cell death and tumor suppression mechanism.

scholarly journals Atorvastatin Inhibits Breast Cancer Cells by Downregulating PTEN/AKT Pathway via Promoting Ras Homolog Family Member B (RhoB)

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Qing Ma ◽  
Yang Gao ◽  
Pei Xu ◽  
Kai Li ◽  
Xiaolong Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Family Member ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Akt Pathway ◽  
Altered Expression ◽  
Breast Tumor Cells ◽  
Cancer Tissues

Background. Breast cancer (BC) is one of the most common malignant tumors in women around the world. Atorvastatin (ATO) was found to be associated with a decreased risk of recurrence and mortality in cancer. But the exact mechanism of its carcinostatic effects is unclear. The expression level of Ras homolog family member B (RhoB) in breast cancer cells was found to be upregulated after being treated with ATO. Thus, we conjecture that altered expression of RhoB induced by ATO may be decisive for the migration and progression of breast cancer. Methods. The effects of ATO on breast tumor cells in vivo and in vitro were detected by clone formation assay, CCK-8 assay, flow cytometry, wound healing, transwell assays, tumor xenograft model, and immunohistochemistry. Distribution of RhoB in different breast cancer tissues and its influence on prognosis were analyzed using the data from TCGA or GEO databases. The relationship between RhoB and PTEN/AKT pathway was detected by Western blotting and RT-qPCR. Results. ATO inhibits proliferation, invasion, EMT, and PTEN/AKT pathway and promotes apoptosis in breast tumor cells. In addition, ATO inhibits the volume and weight of breast tumor in tumor-bearing mice and upregulated RhoB in tumor tissues. The expression of RhoB in mRNA and protein level was upregulated in statin-treated breast cancer cells and downregulated in cancer tissues. Low expression of RhoB links with poor prognosis in patients with breast cancer (HR = 0.74[0.66–0.83], p =7e−8, log-rank test). Further research found that RhoB inhibits the proliferation, invasion, EMT, and PTEN/AKT signal pathway in breast tumor cells. Conclusions. The exact mechanism of ATO’s carcinostatic effects in breast cancer is related to downregulating PTEN/AKT pathway via promoting RhoB. Our study also demonstrates the potential applicability of RhoB as a therapeutic target for breast cancer.

scholarly journals KCa3.1 Channels Confer Radioresistance to Breast Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1285 ◽  
Author(s):  
Mohr ◽  
Gross ◽  
Sezgin ◽  
Steudel ◽  
Ruth ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Therapy Response ◽  
Orthotopic Mouse Model ◽  
Breast Tumor Cells ◽  
Fractionated Radiotherapy

KCa3.1 K+ channels reportedly contribute to the proliferation of breast tumor cells and may serve pro-tumor functions in the microenvironment. The putative interaction of KCa3.1 with major anti-cancer treatment strategies, which are based on cytotoxic drugs or radiotherapy, remains largely unexplored. We employed KCa3.1-proficient and -deficient breast cancer cells derived from breast cancer-prone MMTV-PyMT mice, pharmacological KCa3.1 inhibition, and a syngeneic orthotopic mouse model to study the relevance of functional KCa3.1 for therapy response. The KCa3.1 status of MMTV-PyMT cells did not determine tumor cell proliferation after treatment with different concentrations of docetaxel, doxorubicin, 5-fluorouracil, or cyclophosphamide. KCa3.1 activation by ionizing radiation (IR) in breast tumor cells in vitro, however, enhanced radioresistance, probably via an involvement of the channel in IR-stimulated Ca2+ signals and DNA repair pathways. Consistently, KCa3.1 knockout increased survival time of wildtype mice upon syngeneic orthotopic transplantation of MMTV-PyMT tumors followed by fractionated radiotherapy. Combined, our results imply that KCa3.1 confers resistance to radio- but not to chemotherapy in the MMTV-PyMT breast cancer model. Since KCa3.1 is druggable, KCa3.1 targeting concomitant to radiotherapy seems to be a promising strategy to radiosensitize breast tumors.

Expression of Toll like Receptor 4 in the ductal epithelial cells of the Breast tumor microenvironment is correlated with the invasiveness of the tumor

2020 ◽  
Author(s):  
Anuradha Moirangthem ◽  
Mala Mukherjee ◽  
Banashree Bondhopadhyay ◽  
Arghya Bandyopadhyay ◽  
Narendranath Mukherjee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Tlr4 Expression ◽  
Toll Like Receptors ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

AbstractToll like receptors are expressed by variety of cells, mainly immune cells and also found to have role in the tumor microenvironment. Among them, Toll like receptors-4 is found to modulate tumor progression. But definitive action of TLR4 in tumor progression is not well understood. In the present study, in breast tumor samples, expression of TLR4 was studied by immunohistochemistry method while MMP2 and MMP9 expression were studied by gelatin zymography. Kaplan Meier plotter was used to test survivability. Breast cancer cells - MCF7, MDA MB 231, T47D were studied in the presence of TLR4 lignd LPS, with the help of MTT assay, BrdU incorporation assay, scratch wound healing assay and invasion assay. Activation of TLR4 in MCF7 which is TP53 wild type has no significant effect in proliferative rate, adhesiveness and invasiveness. While in MDA-MB-231 and T47D which are TP53 mutant, there were a significant increase in adhesiveness and migratory ability, observed., TLR4 had been expressed in breast tumor of invasive ductal carcinoma (IDC) and was found to be significantly correlated with lymph node involvement. Kaplan Meier plotter analysis revealed that high TLR4 expression might serve as an immune-protectant in invading cancer cells of TP53 wild state. It has been revealed that activation of TLR4 in breast cancer cells leads to higher expression of EMT related genes along with matrix metalloproteinases helping in migration and invasion of cells. Kaplan Meier plotter analysis revealed that TP53 wild status of the patient along with high TLR4 expression has a good overall survival of the patients.

scholarly journals ANGPTL2 increases bone metastasis of breast cancer cells through enhancing CXCR4 signaling

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Tetsuro Masuda ◽  
Motoyoshi Endo ◽  
Yutaka Yamamoto ◽  
Haruki Odagiri ◽  
Tsuyoshi Kadomatsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Cxcr4 Expression ◽  
Breast Cancer Patients

Abstract Bone metastasis of breast cancer cells is a major concern, as it causes increased morbidity and mortality in patients. Bone tissue-derived CXCL12 preferentially recruits breast cancer cells expressing CXCR4 to bone metastatic sites. Thus, understanding how CXCR4 expression is regulated in breast cancer cells could suggest approaches to decrease bone metastasis of breast tumor cells. Here, we show that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) increases responsiveness of breast cancer cells to CXCL12 by promoting up-regulation of CXCR4 in those cells. In addition, we used a xenograft mouse model established by intracardiac injection of tumor cells to show that ANGPTL2 knockdown in breast cancer cells attenuates tumor cell responsiveness to CXCL12 by decreasing CXCR4 expression in those cells, thereby decreasing bone metastasis. Finally, we found that ANGPTL2 and CXCR4 expression levels within primary tumor tissues from breast cancer patients are positively correlated. We conclude that tumor cell-derived ANGPTL2 may increase bone metastasis by enhancing breast tumor cell responsiveness to CXCL12 signaling through up-regulation of tumor cell CXCR4 expression. These findings may suggest novel therapeutic approaches to treat metastatic breast cancer.

scholarly journals Cyclin D1 triggers autonomous growth of breast cancer cells by governing cell cycle exit.

1996 ◽  
Vol 16 (6) ◽  
pp. 2554-2560 ◽  
Author(s):  
R M Zwijsen ◽  
R Klompmaker ◽  
E B Wientjens ◽  
P M Kristel ◽  
B van der Burg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Growth Factor ◽  
Cyclin D1 ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Cell Cycle Exit ◽  
Breast Tumor Cells ◽  
Low Serum

Cyclin D1 controls G1-associated processes, including G0-to-G1 and G1-to-S transitions. This study demonstrates a novel aspect of cyclin D1 as a regulator of the transition between G1 and G0. Overexpression of cyclin D1 in MCF7 breast tumor cells resulted in a continued proliferation under low-serum conditions, whereas nonoverexpressing cells ceased to grow. This difference in growth was due to a reduced exit from G1 to G0 in cyclin D1-overexpressing cells. Our data therefore suggest a model in which cyclin D1 overexpression in tumor cells is responsible for hyperproliferation under growth factor-deprived conditions.

scholarly journals Activating Transcription Factor 4 Promotes Angiogenesis of Breast Cancer through Enhanced Macrophage Recruitment

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Chen Liu ◽  
Zongjin Li ◽  
Lina Wang ◽  
Lingling Tong ◽  
Ningning He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Tumor Angiogenesis ◽  
Breast Cancer Cells ◽  
Activating Transcription Factor 4 ◽  
Tumor Tissues ◽  
Activating Transcription Factor ◽  
Transcription Factor 4

Angiogenesis plays an important role in the progression of tumor. Besides being regulated by tumor cells per se, tumor angiogenesis is also influenced by stromal cells in tumor microenvironment (TME), for example, tumor associated macrophages (TAMs). Activating transcription factor 4 (ATF4), a member of the ATF/CREB family, has been reported to be related to tumor angiogenesis. In this study, we found that exogenous overexpression of ATF4 in mouse breast cancer cells promotes tumor growth via increasing tumor microvascular density. However, ATF4 overexpression failed to increase the expression level of a series of proangiogenic factors including vascular endothelial growth factor A (VEGFA) in tumor cells in this model. Thus, we further investigated the infiltration of proangiogenic macrophages in tumor tissues and found that ATF4-overexpressing tumors could recruit more macrophages via secretion of macrophage colony stimulating factor (M-CSF). Overall, we concluded that exogenous overexpression of ATF4 in breast cancer cells may facilitate the recruitment of macrophages into tumor tissues and promote tumor angiogenesis and tumor growth indirectly.

scholarly journals The Breast Tumor Microenvironment: A Key Player in Metastatic Spread

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4798
Author(s):  
Lucas E. L. Terceiro ◽  
Chidalu A. Edechi ◽  
Nnamdi M. Ikeogu ◽  
Barbara E. Nickel ◽  
Sabine Hombach-Klonisch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Metastatic Spread ◽  
Paracrine Factors ◽  
Primary Tumor Site

The tumor microenvironment plays a pivotal role in the tumorigenesis, progression, and metastatic spread of many cancers including breast. There is now increasing evidence to support the observations that a bidirectional interplay between breast cancer cells and stromal cells exists within the tumor and the tumor microenvironment both at the primary tumor site and at the metastatic site. This interaction occurs through direct cell to cell contact, or by the release of autocrine or paracrine factors which can activate pro-tumor signaling pathways and modulate tumor behavior. In this review, we will highlight recent advances in our current knowledge about the multiple interactions between breast cancer cells and neighboring cells (fibroblasts, endothelial cells, adipocytes, innate and adaptive immune cells) in the tumor microenvironment that coordinate to regulate metastasis. We also highlight the role of exosomes and circulating tumor cells in facilitating breast cancer metastasis. We discuss some key markers associated with stromal cells in the breast tumor environment and their potential to predict patient survival and guide treatment. Finally, we will provide some brief perspectives on how current technologies may lead to the development of more effective therapies for the clinical management of breast cancer patients.

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