Cargando…
The Epigenetic Profile of Tumor Endothelial Cells. Effects of Combined Therapy with Antiangiogenic and Epigenetic Drugs on Cancer Progression
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...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177242/ https://www.ncbi.nlm.nih.gov/pubmed/32283668 http://dx.doi.org/10.3390/ijms21072606 |
_version_ | 1783525175193501696 |
---|---|
author | Ciesielski, Oskar Biesiekierska, Marta Panthu, Baptiste Vialichka, Varvara Pirola, Luciano Balcerczyk, Aneta |
author_facet | Ciesielski, Oskar Biesiekierska, Marta Panthu, Baptiste Vialichka, Varvara Pirola, Luciano Balcerczyk, Aneta |
author_sort | Ciesielski, Oskar |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7177242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71772422020-04-28 The Epigenetic Profile of Tumor Endothelial Cells. Effects of Combined Therapy with Antiangiogenic and Epigenetic Drugs on Cancer Progression Ciesielski, Oskar Biesiekierska, Marta Panthu, Baptiste Vialichka, Varvara Pirola, Luciano Balcerczyk, Aneta Int J Mol Sci Review 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. MDPI 2020-04-09 /pmc/articles/PMC7177242/ /pubmed/32283668 http://dx.doi.org/10.3390/ijms21072606 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Ciesielski, Oskar Biesiekierska, Marta Panthu, Baptiste Vialichka, Varvara Pirola, Luciano Balcerczyk, Aneta The Epigenetic Profile of Tumor Endothelial Cells. Effects of Combined Therapy with Antiangiogenic and Epigenetic Drugs on Cancer Progression |
title | The Epigenetic Profile of Tumor Endothelial Cells. Effects of Combined Therapy with Antiangiogenic and Epigenetic Drugs on Cancer Progression |
title_full | The Epigenetic Profile of Tumor Endothelial Cells. Effects of Combined Therapy with Antiangiogenic and Epigenetic Drugs on Cancer Progression |
title_fullStr | The Epigenetic Profile of Tumor Endothelial Cells. Effects of Combined Therapy with Antiangiogenic and Epigenetic Drugs on Cancer Progression |
title_full_unstemmed | The Epigenetic Profile of Tumor Endothelial Cells. Effects of Combined Therapy with Antiangiogenic and Epigenetic Drugs on Cancer Progression |
title_short | The Epigenetic Profile of Tumor Endothelial Cells. Effects of Combined Therapy with Antiangiogenic and Epigenetic Drugs on Cancer Progression |
title_sort | epigenetic profile of tumor endothelial cells. effects of combined therapy with antiangiogenic and epigenetic drugs on cancer progression |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177242/ https://www.ncbi.nlm.nih.gov/pubmed/32283668 http://dx.doi.org/10.3390/ijms21072606 |
work_keys_str_mv | AT ciesielskioskar theepigeneticprofileoftumorendothelialcellseffectsofcombinedtherapywithantiangiogenicandepigeneticdrugsoncancerprogression AT biesiekierskamarta theepigeneticprofileoftumorendothelialcellseffectsofcombinedtherapywithantiangiogenicandepigeneticdrugsoncancerprogression AT panthubaptiste theepigeneticprofileoftumorendothelialcellseffectsofcombinedtherapywithantiangiogenicandepigeneticdrugsoncancerprogression AT vialichkavarvara theepigeneticprofileoftumorendothelialcellseffectsofcombinedtherapywithantiangiogenicandepigeneticdrugsoncancerprogression AT pirolaluciano theepigeneticprofileoftumorendothelialcellseffectsofcombinedtherapywithantiangiogenicandepigeneticdrugsoncancerprogression AT balcerczykaneta theepigeneticprofileoftumorendothelialcellseffectsofcombinedtherapywithantiangiogenicandepigeneticdrugsoncancerprogression AT ciesielskioskar epigeneticprofileoftumorendothelialcellseffectsofcombinedtherapywithantiangiogenicandepigeneticdrugsoncancerprogression AT biesiekierskamarta epigeneticprofileoftumorendothelialcellseffectsofcombinedtherapywithantiangiogenicandepigeneticdrugsoncancerprogression AT panthubaptiste epigeneticprofileoftumorendothelialcellseffectsofcombinedtherapywithantiangiogenicandepigeneticdrugsoncancerprogression AT vialichkavarvara epigeneticprofileoftumorendothelialcellseffectsofcombinedtherapywithantiangiogenicandepigeneticdrugsoncancerprogression AT pirolaluciano epigeneticprofileoftumorendothelialcellseffectsofcombinedtherapywithantiangiogenicandepigeneticdrugsoncancerprogression AT balcerczykaneta epigeneticprofileoftumorendothelialcellseffectsofcombinedtherapywithantiangiogenicandepigeneticdrugsoncancerprogression |