Hydrogen peroxide regulates angiogenesis-related factors in tumor cells

2017 ◽  
Vol 95 (6) ◽  
pp. 679-685 ◽  
Author(s):  
Ana Jerónimo ◽  
Gonçalo Rodrigues ◽  
Filipe Vilas-Boas ◽  
Gabriel G. Martins ◽  
Ana Bagulho ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Tumor Angiogenesis ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Angiogenic Factors ◽  
Related Factors ◽  
Tumor Neovascularization ◽  
A Cell ◽  
Vessel Network ◽  
Xenografted Tumor

Tumor angiogenesis is required for tumor development and growth, and is regulated by several factors including ROS. H2O2 is a ROS with an important role in cell signaling, but how H2O2 regulates tumor angiogenesis is still poorly understood. We have xenografted tumor cells with altered levels of H2O2 by catalase overexpression into zebrafish embryos to study redox-induced tumor neovascularization. We found that vascular recruitment and invasion were impaired if catalase was overexpressed. In addition, the overexpression of catalase altered the transcriptional levels of several angiogenesis-related factors in tumor cells, including TIMP-3 and THBS1. These two anti-angiogenic factors were found to be H2O2-regulated by two different mechanisms: TIMP-3 expression in a cell-autonomous manner; and, THBS1 expression that was non-cell-autonomous. Our work shows that intracellular H2O2 regulates the expression of angiogenic factors and the formation of a vessel network. Understanding the molecular mechanisms that govern this multifunctional effect of H2O2 on tumor angiogenesis could be important for the development of more efficient anti-angiogenic therapies.

scholarly journals The role of microenvironment in tumor angiogenesis

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Xianjie Jiang ◽  
Jie Wang ◽  
Xiangying Deng ◽  
Fang Xiong ◽  
Shanshan Zhang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Tumor Angiogenesis ◽  
Tumor Development ◽  
Invasion And Metastasis ◽  
Growth And Survival ◽  
Survival And Development ◽  
Inflammatory Drugs ◽  
Conducive Environment

Abstract Tumor angiogenesis is necessary for the continued survival and development of tumor cells, and plays an important role in their growth, invasion, and metastasis. The tumor microenvironment—composed of tumor cells, surrounding cells, and secreted cytokines—provides a conducive environment for the growth and survival of tumors. Different components of the tumor microenvironment can regulate tumor development. In this review, we have discussed the regulatory role of the microenvironment in tumor angiogenesis. High expression of angiogenic factors and inflammatory cytokines in the tumor microenvironment, as well as hypoxia, are presumed to be the reasons for poor therapeutic efficacy of current anti-angiogenic drugs. A combination of anti-angiogenic drugs and antitumor inflammatory drugs or hypoxia inhibitors might improve the therapeutic outcome.

scholarly journals Centrosome Clustering in the Development of Bovine Binucleate Trophoblast Giant Cells

2016 ◽  
Vol 203 (5) ◽  
pp. 287-294 ◽  
Author(s):  
Karl Klisch ◽  
Elisabeth M. Schraner ◽  
Alois Boos
Keyword(s):  
Cell Cycle ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Giant Cells ◽  
Cell Nuclei ◽  
Pericentriolar Material ◽  
A Cell ◽  
Pass Through ◽  
Diploid Cells ◽  
Trophoblast Giant Cells

Binucleate trophoblast giant cells (BNC) are the characteristic feature of the ruminant placenta. During their development, BNC pass through 2 acytokinetic mitoses and become binucleate with 2 tetraploid nuclei. In this study, we investigate the number and location of centrosomes in bovine BNC. Centrosomes typically consist of 2 centrioles surrounded by electron-dense pericentriolar material. Duplication of centrosomes is tightly linked to the cell cycle, which ensures that the number of centrosomes remains constant in proliferating diploid cells. Alterations of the cell cycle, which affect the number of chromosome sets, also affect the number of centrosomes. In this study, we use placentomal tissue from pregnant cows (gestational days 80-230) for immunohistochemical staining of γ-tubulin (n = 3) and transmission electron microscopy (n = 3). We show that mature BNC have 4 centrosomes with 8 centrioles, clustered in the angle between the 2 cell nuclei. During the second acytokinetic mitosis, the centrosomes must be clustered to form the poles of a bipolar spindle. In rare cases, centrosome clustering fails and tripolar mitosis leads to the formation of trinucleate “BNC”. Generally, centrosome clustering occurs in polyploid tumor cells, which have an increased number of centrioles, but it is absent in proliferating diploid cells. Thus, inhibition of centrosome clustering in tumor cells is a novel promising strategy for cancer treatment. BNC are a cell population in which centrosome clustering occurs as part of the normal life history. Thus, they might be a good model for the study of the molecular mechanisms of centrosome clustering.

scholarly journals The Interaction Between Long Non-Coding RNAs and Cancer-Associated Fibroblasts in Lung Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Wenqi Ti ◽  
Jianbo Wang ◽  
Yufeng Cheng
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Cancer Associated Fibroblasts ◽  
Protein Coding ◽  
Sequencing Technologies ◽  
Integral Role ◽  
Tumor Growth And Metastasis

Despite great advances in research and treatment, lung cancer is still one of the most leading causes of cancer-related deaths worldwide. Evidence is mounting that dynamic communication network in the tumor microenvironment (TME) play an integral role in tumor initiation and development. Cancer-associated fibroblasts (CAFs), which promote tumor growth and metastasis, are the most important stroma component in the tumor microenvironment. Consequently, in-depth identification of relevant molecular mechanisms and biomarkers related to CAFs will increase understanding of tumor development process, which is of great significance for precise treatment of lung cancer. With the development of sequencing technologies such as microarray and next-generation sequencing, lncRNAs without protein-coding ability have been found to act as communicators between tumor cells and CAFs. LncRNAs participate in the activation of normal fibroblasts (NFs) to CAFs. Moreover, activated CAFs can influence the gene expression and secretion characteristics of cells through lncRNAs, enhancing the malignant biological process in tumor cells. In addition, lncRNA-loaded exosomes are considered to be another important form of crosstalk between tumor cells and CAFs. In this review, we focus on the interaction between tumor cells and CAFs mediated by lncRNAs in the lung cancer microenvironment, and discuss the analysis of biological function and molecular mechanism. Furthermore, it contributes to paving a novel direction for the clinical treatment of lung cancer.

scholarly journals Could Extracellular Vesicles Contribute to Generation or Awakening of “Sleepy” Metastatic Niches?

2021 ◽  
Vol 9 ◽  
Author(s):  
Alberto Hernández-Barranco ◽  
Laura Nogués ◽  
Héctor Peinado
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Residual Disease ◽  
Tumor Development ◽  
Extracellular Vesicle ◽  
Primary Tumors ◽  
Favorable Conditions ◽  
Cell Dormancy

Pre-metastatic niches provide favorable conditions for tumor cells to disseminate, home to and grow in otherwise unfamiliar and distal microenvironments. Tumor-derived extracellular vesicles are now recognized as carriers of key messengers secreted by primary tumors, signals that induce the formation of pre-metastatic niches. Recent evidence suggests that tumor cells can disseminate from the very earliest stages of primary tumor development. However, once they reach distal sites, tumor cells can persist in a dormant state for long periods of time until their growth is reactivated and they produce metastatic lesions. In this new scenario, the question arises as to whether extracellular vesicles could influence the formation of these metastatic niches with dormant tumor cells? (here defined as “sleepy niches”). If so, what are the molecular mechanisms involved? In this perspective-review article, we discuss the possible influence of extracellular vesicles in early metastatic dissemination and whether they might play a role in tumor cell dormancy. In addition, we comment whether extracellular vesicle-mediated signals may be involved in tumor cell awakening, considering the possibility that extracellular vesicles might serve as biomarkers to detect early metastasis and/or minimal residual disease (MRD) monitoring.

The application of circulating tumor cells detecting methods in veterinary oncology

2013 ◽  
Vol 16 (1) ◽  
pp. 141-151 ◽  
Author(s):  
M. Chmielewska ◽  
K. Łosiewicz ◽  
P. Socha ◽  
T. Męcik-Kronenberg ◽  
K. Wąsowicz
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Detection Methods ◽  
Patient Death ◽  
Optimal Method ◽  
Early Disease Detection ◽  
Metastasis Development ◽  
Diagnosis Of Cancer

Abstract Cancers are one of the most common diseases affecting dogs. Many of them develop spontaneously and their biology and histopathology shows many similarities to human cancers. What more, it is proved that there are much more analogies in molecular mechanisms of cancer development between these two species. Human oncology is seeking more and more efficient methods for an early disease detection which results directly in the extended life expectancy of patients affected. One of the most modern trends in the diagnosis of cancer is to detect circulating tumor cells (CTC) in the blood of patients. It is known that these cells are responsible for the formation of metastases in distant organs what results in the patient death. Moreover, it’s confirmed that CTC are already present in patients’ bloodstream in the early stages of tumor development. There is no doubt that mechanism of metastasis development in dogs is identical and thus the CTC are also present in their bloodstream. Despite the intense researches there is still no optimal method of isolating cancer cells from the blood where they occur extremely rarely. The purpose of this study is to analyze the implications of the detection methods of tumor cells in the blood in veterinary oncology.

scholarly journals The Crosstalk between Tumor Cells and the Microenvironment in Hepatocellular Carcinoma: The Role of Exosomal microRNAs and Their Clinical Implications

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 823 ◽  
Author(s):  
Devis Pascut ◽  
Muhammad Yogi Pratama ◽  
Niem V.T. Vo ◽  
Rina Masadah ◽  
Claudio Tiribelli
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Immune Escape ◽  
Tumor Development ◽  
Multi Drug Resistance ◽  
Mesenchymal Transition ◽  
Molecular Aspects

The communication between hepatocellular carcinoma (HCC) cells and their microenvironment is an essential mechanism supporting or preventing tumor development and progression. Recent evidence has identified extracellular vesicles (EVs) as one of the mechanisms mediating paracrine signaling between cells. Exosomes, the most described class of EVs, deliver proteins, mRNAs, noncoding RNAs, DNA, and lipids to recipient cells, also at remote distances. MicroRNAs (miRNAs), as part of the non-coding RNA exosomal cargo, have an important role in regulating cellular pathways in targeted cells, regulating several processes related to tumor progression invasion and metastasis, such as angiogenesis, immune-escape, epithelial-to-mesenchymal transition, invasion, and multi-drug resistance. Accumulating evidence suggests exosomal miRNAs as relevant players in the dynamic crosstalk among cancerous, immune, and stromal cells in establishing the tumorigenic microenvironment. In addition, they sustain the metastasic niche formation at distant sites. In this review, we summarized the recent findings on the role of the exosome-derived miRNAs in the cross-communication between tumor cells and different hepatic resident cells, with a focus on the molecular mechanisms responsible for the cell re-programming. In addition, we describe the clinical implication derived from the exosomal miRNA-driven immunomodulation to the current immunotherapy strategies and the molecular aspects influencing the resistance to therapeutic agents.

scholarly journals Patterns of tumor progression predict small and tissue-specific tumor-originating niches

2018 ◽  
Author(s):  
Thomas Buder ◽  
Andreas Deutsch ◽  
Barbara Klink ◽  
Anja Voss-Böhme
Keyword(s):  
Tumor Cells ◽  
Malignant Tumors ◽  
Tumor Development ◽  
Tumor Formation ◽  
Tissue Type ◽  
Human Tissues ◽  
Cell Type ◽  
Tissue Specific ◽  
Specific Tumor ◽  
A Cell

AbstractCancer development is a multistep process in which cells increase in malignancy through progressive alterations. The early phase of this process is hardly observable which aggravates an understanding of later tumor development. We shed light on this initial phase with a cell-based stochastic model calibrated with epidemiological data from the tissue scale. Our model allows to estimate the number of tumor cells needed for tumor formation in human tissues based on data on the diagnosed ratios of benign and malignant tumors. We find that the minimal number of cells needed for tumor formation is surprisingly small and largely depends on the tissue type. Our results point towards the existence of tumor-originating niches in which the fate of tumor development is early decided. Our estimate for the human colon agrees well with the size of the stem cell niche in colonic crypts. Our estimates might help to identify the tumor-originating cell type, e.g. our analysis suggests for glioblastoma that the tumors originate from a cell type competing in a range of 300 - 1900 cells.SummaryWe estimate the number of tumor cells needed for tumor formation in human tissues and propose the existence of small and tissue-specific tumor-originating niches which might help to find tumor-originating cell types, in particular in glioblastoma.

scholarly journals Mesothelioma Malignancy and the Microenvironment: Molecular Mechanisms

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5664
Author(s):  
Francesca Cersosimo ◽  
Marcella Barbarino ◽  
Silvia Lonardi ◽  
William Vermi ◽  
Antonio Giordano ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Asbestos Exposure ◽  
Treatment Options ◽  
Tumor Development ◽  
Asbestos Fibers ◽  
Bidirectional Communication ◽  
Druggable Targets

Several studies have reported that cellular and soluble components of the tumor microenvironment (TME) play a key role in cancer-initiation and progression. Considering the relevance and the complexity of TME in cancer biology, recent research has focused on the investigation of the TME content, in terms of players and informational exchange. Understanding the crosstalk between tumor and non-tumor cells is crucial to design more beneficial anti-cancer therapeutic strategies. Malignant pleural mesothelioma (MPM) is a complex and heterogenous tumor mainly caused by asbestos exposure with few treatment options and low life expectancy after standard therapy. MPM leukocyte infiltration is rich in macrophages. Given the failure of macrophages to eliminate asbestos fibers, these immune cells accumulate in pleural cavity leading to the establishment of a unique inflammatory environment and to the malignant transformation of mesothelial cells. In this inflammatory landscape, stromal and immune cells play a driven role to support tumor development and progression via a bidirectional communication with tumor cells. Characterization of the MPM microenvironment (MPM-ME) may be useful to understand the complexity of mesothelioma biology, such as to identify new molecular druggable targets, with the aim to improve the outcome of the disease. In this review, we summarize the known evidence about the MPM-ME network, including its prognostic and therapeutic relevance.

scholarly journals Bidirectional and Opposite Effects of Naïve Mesenchymal Stem Cells Ontumor Growth and Progression

2019 ◽  
Vol 9 (4) ◽  
pp. 539-558 ◽  
Author(s):  
Faramarz Rahmatizadeh ◽  
Shiva Gholizadeh-Ghaleh Aziz ◽  
Khodadad Khodadadi ◽  
Maryam Lale Ataei ◽  
Esmaeil Ebrahimie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Tumor Stroma ◽  
Cell Types ◽  
Great Promise ◽  
Tumor Tissues ◽  
Essential Components

Cancer has long been considered as a heterogeneous population of uncontrolled proliferation ofdifferent transformed cell types. The recent findings concerning tumorigeneses have highlightedthe fact that tumors can progress through tight relationships among tumor cells, cellular, andnon-cellular components which are present within tumor tissues. In recent years, studies haveshown that mesenchymal stem cells (MSCs) are essential components of non-tumor cells withinthe tumor tissues that can strongly affect tumor development. Several forms of MSCs have beenidentified within tumor stroma. Naïve (innate) mesenchymal stem cells (N-MSCs) derived fromdifferent sources are mostly recruited into the tumor stroma. N-MSCs exert dual and divergenteffects on tumor growth through different conditions and factors such as toll-like receptorpriming (TLR-priming), which is the primary underlying causes of opposite effects. Moreover,MSCs also have the contrary effects by various molecular mechanisms relying on direct cellto-cell connections and indirect communications through the autocrine, paracrine routes, andtumor microenvironment (TME).Overall, cell-based therapies will hold great promise to provide novel anticancer treatments.However, the application of intact MSCs in cancer treatment can theoretically cause adverseclinical outcomes. It is essential that to extensively analysis the effective factors and conditionsin which underlying mechanisms are adopted by MSCs when encounter with cancer.The aim is to review the cellular and molecular mechanisms underlying the dual effects ofMSCs followed by the importance of polarization of MSCs through priming of TLRs.<br />

scholarly journals Significance of Immunosuppressive Cells as a Target for Immunotherapies in Melanoma and Non-Melanoma Skin Cancers

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1087 ◽  
Author(s):  
Taku Fujimura ◽  
Setsuya Aiba
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Tumor Development ◽  
Suppressor Cells ◽  
Related Factors ◽  
Skin Cancers ◽  
Immunosuppressive Tumor Microenvironment ◽  
Immunosuppressive Cells ◽  
Promote Tumor Development

Tumor-associated macrophages (TAMs) have been detected in most skin cancers. TAMs produce various chemokines and angiogenic factors that promote tumor development, along with other immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and tumor-associated neutrophils. TAMs generated from monocytes develop into functional, fully activated macrophages, and TAMs obtain various immunosuppressive functions to maintain the tumor microenvironment. Since TAMs express PD1 to maintain the immunosuppressive M2 phenotype by PD1/PD-L1 signaling from tumor cells, and the blockade of PD1/PD-L1 signaling by anti-PD1 antibodies (Abs) activate and re-polarize TAMs into immunoreactive M1 phenotypes, TAMs represent a potential target for anti-PD1 Abs. The main population of TAMs comprises CD163+ M2 macrophages, and CD163+ TAMs release soluble (s)CD163 and several proinflammatory chemokines (CXCL5, CXCL10, CCL19, etc.) as a result of TAM activation to induce an immunosuppressive tumor microenvironment together with other immunosuppressive cells. Since direct blockade of PD1/PD-L1 signaling between tumor cells and tumor-infiltrating T cells (both effector T cells and Tregs) is mandatory for inducing an anti-immune response by anti-PD1 Abs, anti-PD1 Abs need to reach the tumor microenvironment to induce anti-immune responses in the tumor-bearing host. Taken together, TAM-related factors could offer a biomarker for anti-PD1 Ab-based immunotherapy. Understanding the crosstalk between TAMs and immunosuppressive cells is important for optimizing PD1 Ab-based immunotherapy.

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