scholarly journals The Epigenetic Profile of Tumor Endothelial Cells. Effects of Combined Therapy with Antiangiogenic and Epigenetic Drugs on Cancer Progression

2020 ◽  
Vol 21 (7) ◽  
pp. 2606 ◽  
Author(s):  
Oskar Ciesielski ◽  
Marta Biesiekierska ◽  
Baptiste Panthu ◽  
Varvara Vialichka ◽  
Luciano Pirola ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Blood Vessels ◽  
Cancer Progression ◽  
Combined Therapy ◽  
Angiogenic Factors ◽  
Angiogenic Switch ◽  
Tumor Endothelial Cells ◽  
Antiangiogenic Factors ◽  
Tumor Blood Vessels

Tumors require a constant supply of nutrients to grow which are provided through tumor blood vessels. To metastasize, tumors need a route to enter circulation, that route is also provided by tumor blood vessels. Thus, angiogenesis is necessary for both tumor progression and metastasis. Angiogenesis is tightly regulated by a balance of angiogenic and antiangiogenic factors. Angiogenic factors of the vascular endothelial growth factor (VEGF) family lead to the activation of endothelial cells, proliferation, and neovascularization. Significant VEGF-A upregulation is commonly observed in cancer cells, also due to hypoxic conditions, and activates endothelial cells (ECs) by paracrine signaling stimulating cell migration and proliferation, resulting in tumor-dependent angiogenesis. Conversely, antiangiogenic factors inhibit angiogenesis by suppressing ECs activation. One of the best-known anti-angiogenic factors is thrombospondin-1 (TSP-1). In pathological angiogenesis, the balance shifts towards the proangiogenic factors and an angiogenic switch that promotes tumor angiogenesis. Here, we review the current literature supporting the notion of the existence of two different endothelial lineages: normal endothelial cells (NECs), representing the physiological form of vascular endothelium, and tumor endothelial cells (TECs), which are strongly promoted by the tumor microenvironment and are biologically different from NECs. The angiogenic switch would be also important for the explanation of the differences between NECs and TECs, as angiogenic factors, cytokines and growth factors secreted into the tumor microenvironment may cause genetic instability. In this review, we focus on the epigenetic differences between the two endothelial lineages, which provide a possible window for pharmacological targeting of TECs.

scholarly journals Tumor Endothelial Heterogeneity in Cancer Progression

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1511 ◽  
Author(s):  
Nako Maishi ◽  
Dorcas A. Annan ◽  
Hiroshi Kikuchi ◽  
Yasuhiro Hida ◽  
Kyoko Hida
Keyword(s):  
Tumor Microenvironment ◽  
Blood Vessels ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Phenotypic Diversity ◽  
Expression Patterns ◽  
Specific Gene ◽  
Endothelial Heterogeneity ◽  
Tumor Blood Vessels ◽  
And Migration

Tumor blood vessels supply nutrients and oxygen to tumor cells for their growth and provide routes for them to enter circulation. Thus, angiogenesis, the formation of new blood vessels, is essential for tumor progression and metastasis. Tumor endothelial cells (TECs) that cover the inner surfaces of tumor blood vessels reportedly show phenotypes distinct from those of their normal counterparts. As examples, TECs show cytogenetic abnormalities, resistance to anticancer drugs, activated proliferation and migration, and specific gene expression patterns. TECs contain stem-like cell populations, which means that the origin of TECs is heterogeneous. In addition, since some abnormal phenotypes in TECs are induced by factors in the tumor microenvironment, such as hypoxia and tumor cell-derived factors, phenotypic diversity in TECs may be caused in part by intratumoral heterogeneity. Recent studies have identified that the interaction of tumor cells and TECs by juxtacrine and paracrine signaling contributes to tumor malignancy. Understanding TEC abnormality and heterogeneity is important for treatment of cancers. This review provides an overview of the diversity of TECs and discusses the interaction between TECs and tumor cells in the tumor microenvironment.

scholarly journals A New Antitumor Direction: Tumor-Specific Endothelial Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Jing Liang ◽  
Shouqi Wang ◽  
Guowei Zhang ◽  
Baoyu He ◽  
Qingli Bie ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Side Effects ◽  
Tumor Microenvironment ◽  
Blood Vessels ◽  
Antiangiogenic Therapy ◽  
Clinical Effects ◽  
Antiangiogenic Drugs ◽  
Tumor Blood Vessels ◽  
New Treatment

Targeting tumor blood vessels is an important strategy for tumor therapies. At present, antiangiogenic drugs are known to have significant clinical effects, but severe drug resistance and side effects also occur. Therefore, new specific targets for tumor and new treatment methods must be developed. Tumor-specific endothelial cells (TECs) are the main targets of antiangiogenic therapy. This review summarizes the differences between TECs and normal endothelial cells, assesses the heterogeneity of TECs, compares tumorigenesis and development between TECs and normal endothelial cells, and explains the interaction between TECs and the tumor microenvironment. A full and in-depth understanding of TECs may provide new insights for specific antitumor angiogenesis therapies.

Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs

2019 ◽  
Vol 41 (5) ◽  
pp. 666-677 ◽  
Author(s):  
Lavinia Raimondi ◽  
Angela De Luca ◽  
Alessia Gallo ◽  
Viviana Costa ◽  
Giovanna Russelli ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Umbilical Vein ◽  
Bioinformatic Analysis ◽  
Micro Rna ◽  
Molecular Profile ◽  
Small Rna Sequencing ◽  
Osteosarcoma Cell ◽  
Illumina Platform

Abstract Bone microenvironment provides growth and survival signals essential for osteosarcoma (OS) initiation and progression. OS cells regulate communications inside tumor microenvironment through different ways and, among all, tumor-derived exosomes support cancer progression and metastasis. To define the contribution of OS-derived exosomes inside the microenvironment, we investigated the effects induced in bone remodeling mechanism and tumor angiogenesis. We demonstrated that exosomes promoted osteoclasts differentiation and bone resorption activity. Furthermore, exosomes potentiated tube formation of endothelial cells and increased angiogenic markers expression. We therefore investigated the micro RNA (miRNA) cargo from exosomes and their parental cells by performing small RNA sequencing through NGS Illumina platform. Hierarchical clustering highlighted a unique molecular profile of exosomal miRNA; bioinformatic analysis by DIANA-mirPath revealed that miRNAs identified take part in various biological processes and carcinogenesis. Among these miRNAs, some were already known for their involvement in the tumor microenvironment establishment, as miR-148a and miR-21-5p. Enforced expression of miR-148a and miR-21-5p in Raw264.7 and hTert immortalized umbilical vein endothelial cells recapitulated the effects induced by exosomes. Overall, our study highlighted the importance of OS exosomes in tumor microenvironment also by a specific packaging of miRNAs.

scholarly journals Alternative Strategies to Inhibit Tumor Vascularization

2019 ◽  
Vol 20 (24) ◽  
pp. 6180 ◽  
Author(s):  
Alessia Brossa ◽  
Lola Buono ◽  
Sofia Fallo ◽  
Alessandra Fiorio Pla ◽  
Luca Munaron ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Tumor Microenvironment ◽  
Tumor Vasculature ◽  
Cell Phenotype ◽  
Tumor Vascularization ◽  
Alternative Strategies ◽  
Tumor Endothelial Cells ◽  
Alternative Approach ◽  
Different Origin

Endothelial cells present in tumors show different origin, phenotype, and genotype with respect to the normal counterpart. Various mechanisms of intra-tumor vasculogenesis sustain the complexity of tumor vasculature, which can be further modified by signals deriving from the tumor microenvironment. As a result, resistance to anti-VEGF therapy and activation of compensatory pathways remain a challenge in the treatment of cancer patients, revealing the need to explore alternative strategies to the classical anti-angiogenic drugs. In this review, we will describe some alternative strategies to inhibit tumor vascularization, including targeting of antigens and signaling pathways overexpressed by tumor endothelial cells, the development of endothelial vaccinations, and the use of extracellular vesicles. In addition, anti-angiogenic drugs with normalizing effects on tumor vessels will be discussed. Finally, we will present the concept of endothelial demesenchymalization as an alternative approach to restore normal endothelial cell phenotype.

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