scholarly journals Review of Mathematical Modelling Techniques in Breast Cancer Dynamics

2021 ◽  
pp. 1-9
Author(s):  
Mashasha Maxwell ◽  
◽  
Chigidi Esther ◽  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Selective Advantage ◽  
Tumor Formation ◽  
Computational Techniques ◽  
Non Invasive ◽  
Age Related ◽  
Modelling Techniques ◽  
Level Of Understanding ◽  
Cancer Dynamics

Cancer is an age related autoimmune disease initiated by genetic mutations leading to increased proliferation rate and tumor formation. Accumulation of various genetic and epigenetic changes, in normal cells gives cancer cells a selective advantage over healthy cells, and lead to cancer initiation and progression. Interactions of tumor cells with other cells within their reach, the microenvironment, is an important component in carcinogenesis. Its treatment is based on our level of understanding of its biology. Breast cancer is a collection of complex and heterogeneous diseases with distinct histopathological features. It arises due to abnormal growths of the cells lining the breast lobules hence men and women can develop it, although very rare in men (less than ). There are different types of breast cancer, and the most common are the invasive and non-invasive cancers. Usually, it is common to study breast cancer tumors as isolated entities, but its biological and molecular structure are indicative of an unstable heterogeneous disease with multiple subtypes coexisting within a tumor. Many studies with different methodologies have been carried out to understand cancer development and progression, however, another approach of mathematical oncology has emerged. This approach uses mathematical and computational techniques to unpack generation, growth and evolution of cancer cells. With this work we would like to review what has been done by others so as to improve our understanding of cancer dynamics

scholarly journals TLR4 Ligand/H2O2 Enhances TGF-β1 Signaling to Induce Metastatic Potential of Non-Invasive Breast Cancer Cells by Activating Non-Smad Pathways

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e65906 ◽  
Author(s):  
Yuan-Hong Zhou ◽  
Sheng-Jun Liao ◽  
Dong Li ◽  
Jing Luo ◽  
Jing-Jing Wei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Invasive Breast Cancer ◽  
Breast Cancer Cells ◽  
Metastatic Potential ◽  
Non Invasive ◽  
Tlr4 Ligand ◽  
Tgf Β1

scholarly journals DJ-1 Proteoforms in Breast Cancer Cells: The Escape of Metabolic Epigenetic Misregulation

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1968
Author(s):  
Domenica Scumaci ◽  
Erika Olivo ◽  
Claudia Vincenza Fiumara ◽  
Marina La Chimia ◽  
Maria Teresa De Angelis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Glycolytic Flux ◽  
Proliferative Potential ◽  
Moderate Increase ◽  
Reactive Carbonyl Species ◽  
Proteomic Approach ◽  
Age Related

Enhanced glycolysis is a hallmark of breast cancer. In cancer cells, the high glycolytic flux induces carbonyl stress, a damaging condition in which the increase of reactive carbonyl species makes DNA, proteins, and lipids more susceptible to glycation. Together with glucose, methylglyoxal (MGO), a byproduct of glycolysis, is considered the main glycating agent. MGO is highly diffusible, enters the nucleus, and can react with easily accessible lysine- and arginine-rich tails of histones. Glycation adducts on histones undergo oxidization and further rearrange to form stable species known as advanced glycation end-products (AGEs). This modification alters nucleosomes stability and chromatin architecture deconstructing the histone code. Formation of AGEs has been associated with cancer, diabetes, and several age-related diseases. Recently, DJ-1, a cancer-associated protein that protects cells from oxidative stress, has been described as a deglycase enzyme. Although its role in cell survival results still controversial, in several human tumors, its expression, localization, oxidation, and phosphorylation were found altered. This work aimed to explore the molecular mechanism that triggers the peculiar cellular compartmentalization and the specific post-translational modifications (PTM) that, occurring in breast cancer cells, influences the DJ-1 dual role. Using a proteomic approach, we identified on DJ-1 a novel threonine phosphorylation (T125) that was found, by the in-silico tool scansite 4, as part of a putative Akt consensus. Notably, this threonine is in addition to histidine 126, a key residue involved in the formation of catalytic triade (glu18-Cys106-His126) inside the glioxalase active site of DJ. Interestingly, we found that pharmacological modulation of Akt pathway induces a functional tuning of DJ-1 proteoforms, as well as their shuttle from cytosol to nucleus, pointing out that pathway as critical in the development of DJ-1 pro-tumorigenic abilities. Deglycase activity of DJ-1 on histones proteins, investigated by coupling 2D tau gel with LC-MS/MS and 2D-TAU (Triton-Acid-Urea)-Western blot, was found correlated with its phosphorylation status that, in turn, depends from Akt activation. In normal conditions, DJ-1 acts as a redox-sensitive chaperone and as an oxidative stress sensor. In cancer cells, glycolytic rewiring, inducing increased reactive oxygen species (ROS) levels, enhances AGEs products. Alongside, the moderate increase of ROS enhances Akt signaling that induces DJ-1-phosphorylation. When phosphorylated DJ-1 increases its glyoxalase activity, the level of AGEs on histones decreases. Therefore, phospho-DJ-1 prevents glycation-induced histones misregulation and its Akt-related hyperactivity represents a way to preserve the epigenome landscape sustaining proliferation of cancer cells. Together, these results shed light on an interesting mechanism that cancer cells might execute to escape the metabolic induced epigenetic misregulation that otherwise could impair their malignant proliferative potential.

scholarly journals Tumor Cell Associated Hyaluronan-CD44 Signaling Promotes Pro-Tumor Inflammation in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1325 ◽  
Author(s):  
Patrice M. Witschen ◽  
Thomas S. Chaffee ◽  
Nicholas J. Brady ◽  
Danielle N. Huggins ◽  
Todd P. Knutson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Chronic Wound ◽  
Gene Signature ◽  
Tumor Formation ◽  
Human Breast ◽  
Inflammatory Microenvironment ◽  
Tumor Types

Cancer has been conceptualized as a chronic wound with a predominance of tumor promoting inflammation. Given the accumulating evidence that the microenvironment supports tumor growth, we investigated hyaluronan (HA)-CD44 interactions within breast cancer cells, to determine whether this axis directly impacts the formation of an inflammatory microenvironment. Our results demonstrate that breast cancer cells synthesize and fragment HA and express CD44 on the cell surface. Using RNA sequencing approaches, we found that loss of CD44 in breast cancer cells altered the expression of cytokine-related genes. Specifically, we found that production of the chemokine CCL2 by breast cancer cells was significantly decreased after depletion of either CD44 or HA. In vivo, we found that CD44 deletion in breast cancer cells resulted in a delay in tumor formation and localized progression. This finding was accompanied by a decrease in infiltrating CD206+ macrophages, which are typically associated with tumor promoting functions. Importantly, our laboratory results were supported by human breast cancer patient data, where increased HAS2 expression was significantly associated with a tumor promoting inflammatory gene signature. Because high levels of HA deposition within many tumor types yields a poorer prognosis, our results emphasize that HA-CD44 interactions potentially have broad implications across multiple cancers.

Lentivirus mediated RNA interference of EMMPRIN (CD147) gene inhibits the proliferation, matrigel invasion and tumor formation of breast cancer cells

2016 ◽  
Vol 17 (2) ◽  
pp. 237-247 ◽  
Author(s):  
Jing Yang ◽  
Rong Wang ◽  
Hongjiang Li ◽  
Qing Lv ◽  
Wentong Meng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rna Interference ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumor Formation ◽  
Matrigel Invasion

Noninvasive identification of lineage-specific circular RNA for ER-positive breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3543-3543 ◽  
Author(s):  
Jason Brown ◽  
Palak Shah ◽  
Josh Vo ◽  
Lanbo Xiao ◽  
Yashar Niknafs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Breast Cancer Cells ◽  
Circular Rna ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Non Invasive ◽  
Er Positive ◽  
Positive Breast Cancer

3543 Background: Non-invasive testing in plasma using RNA biomarkers has been limited by exoribonuclease-mediated degradation of RNA. Circular RNA (circRNA) are covalently closed RNA structures that resist this degradation due to their circular structure. Therefore circRNA are more stable than their linear counterparts. CircRNA are formed by alternative backsplicing of the 3’ end of a downstream exon to the 5’ end of an upstream exon. Here, we propose a novel method for non-invasive identification of circRNA and demonstrate circularized forms of several lineage and cancer specific targets for estrogen receptor-positive breast cancer. Methods: Capture RNA sequencing on cancer tissue was previously performed to determine the relative expression of potential circRNA isoforms in breast cancer patients. These isoforms as well as those predicted by intron length were screened using a quantitative PCR-based assay on ER-positive breast cancer cells. RNA extracted from breast cancer cells are exposed to ribonuclease R to demonstrate stability of circRNA. CircRNA derived from targets with known universal expression are used as positive controls as well as for analysis on plasma. Results: We identify the circRNA isoforms with highest expression for five genes, including ESR1, that are differentially expressed in ER-positive breast cancer compared to other cancers and normal breast tissue. We determine that the circRNA corresponding to all five targets is specifically expressed in breast cancer cell lines with at least 1000-fold higher expression than in non-ER positive breast cancer cell lines. We demonstrate that the highest expressing circRNA isoforms are resistant to degradation by ribonuclease R, whereas corresponding linear mRNA is susceptible. We also demonstrate the presence and stability of positive control circRNA in plasma from patients without cancer. Conclusions: CircRNA are promising biomarkers for early non-invasive detection of cancer due to their stability in plasma. This assay reliably detects ER-positive breast cancer specific circRNA, and exoribonuclease resistance has been validated. Application of this diagnostic assay to plasma from breast cancer patients is underway.

Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells

2015 ◽  
Vol 48 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Ewa Kwiatkowska ◽  
Martyna Wojtala ◽  
Agnieszka Gajewska ◽  
Mirosław Soszyński ◽  
Grzegorz Bartosz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Redox Equilibrium ◽  
Non Invasive ◽  
Mcf 7

scholarly journals Non-Invasive Physical Plasma Enhances the Membrane Permeability to Low Molecular Weight Compounds and Subsequently Leads to the Loss of Cellular ATP and the Devitalization of Epithelial Cancer Cells

2021 ◽  
Vol 11 (21) ◽  
pp. 9801
Author(s):  
Caroline Sander ◽  
Andreas Nitsch ◽  
Holger H. H. Erb ◽  
Eva K. Egger ◽  
Lyubomir Haralambiev ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Weight ◽  
Cancer Cells ◽  
Cytoplasmic Membrane ◽  
Reactive Oxygen ◽  
Cell Physiology ◽  
Low Molecular Weight ◽  
Non Invasive ◽  
Low Molecular Weight Compounds ◽  
Physical Plasma

Non-invasive physical plasma (NIPP) achieves biomedical effects primarily through the formation of reactive oxygen and nitrogen species. In clinical use, these species interact with cells of the treated tissue, affecting the cytoplasmic membrane first. The present study investigated the permeability of the cytoplasmic membrane of breast cancer cells with different fluorescent dyes after NIPP treatment and determined the subsequent effects on cell viability. After NIPP treatment and the associated formation of reactive oxygen species, low molecular weight compounds were able to pass through the cytoplasmic membrane in both directions to a higher extent. Consequently, a loss of cellular ATP into the extracellular space was induced. Due to these limitations in cell physiology, apoptosis was induced in the cancer cells and the entire cell population exhibited decreased cell growth. It can be concluded that NIPP treatment disturbs the biochemical functionality of the cytoplasmic membrane of cancer cells, which massively impairs their viability. This observation opens a vast application horizon of NIPP therapy to treat precancerous and malignant diseases beyond breast cancer therapy.

scholarly journals Invadopodia enable cooperative invasion and metastasis of breast cancer cells

2021 ◽  
Author(s):  
Louisiane Perrin ◽  
Battuya Bayarmagnai ◽  
Erkan Tuzel ◽  
Bojana Gligorijevic
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Sorting ◽  
Breast Cancer Cells ◽  
Time Lapse ◽  
Invasion And Metastasis ◽  
Non Invasive ◽  
Syngeneic Mouse Model ◽  
4T1 Cells ◽  
3D Spheroids

Abstract Multiple clones of cancer cells can seed metastases via collective invasion and dissemination. While it is known that cancer clones can cooperate during invasion, the events leading to it and the effects it may have on metastasis are not known. In this study, we demonstrate that, when mixed in 3D spheroids, the isogenic 4T1 and 67NR breast cancer cells sort from each other, followed by their cooperative invasion. By time-lapse microscopy of heterogenous spheroids embedded in collagen I, we show that the invasive 4T1 cells that reach the spheroid edge remain there, while the non-invasive 67NR cells move randomly. This results in cell sorting and enrichment of invasive 4T1 cells at the spheroid periphery. Following cell sorting, 4T1 cells lead the 67NR cells in cooperative invasion. Elimination of invadopodia in 4T1 cells, by knockdown of the protein Tks5, blocks invasion and demonstrates that invasion requires invadopodia only in leader cells and not in follower cells. Importantly, using syngeneic mouse model, we demonstrate that cells with and without invadopodia can also engage in cooperative metastasis. Altogether, our results suggest that a few clones with invadopodia could drive the metastasis of cell clusters from heterogeneous tumors.

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