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.

Analysis of multidrug resistant transporter expression in tumor blood vessels of urothelial carcinoma during chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23004-e23004
Author(s):  
Hiroshi Kikuchi ◽  
Nako Maishi ◽  
Kosuke Akiyama ◽  
Masahiro Morimoto ◽  
Misa Yanagiya ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Blood Vessels ◽  
Tumor Cells ◽  
Cancer Drug ◽  
Cancer Drug Resistance ◽  
Before And After ◽  
Mdr1 Mrna ◽  
Tumor Blood Vessels ◽  
Line Chemotherapy

e23004 Background: ABCB1, a multidrug transporter, is encoded by multidrug resistance (MDR) 1 gene and plays a major role in drug resistance. Recently, we have reported that not only tumor cells, tumor vascular endothelial cells (TECs) also confer cancer drug resistance. We isolated TECs and found that they have various abnormalities such as aneuploidy or stemness characteristics. TECs showed resistance to Paclitaxel (PTX) with ABCB1 up-regulation. Furthermore, their resistance to PTX was abrogated by ABCB1 inhibition of TECs in vivo. In clinical urology, gemcitabine / cisplatin (GC) is standard 1st line chemotherapy for metastatic urothelial carcinoma (mUC). PTX is often selected in 2nd line chemotherapy for GC resistant cases, however the therapeutic outcomes are limited. We hypothesized that ABCB1 inhibitor/PTX combination would be more effective strategy for mUC, if TEC ABCB1 expression is upregulated. In this study, we investigated ABCB1 expression in tumor blood vessels of UC during 1st line chemotherapy. Methods: Paraffin-embedded samples were corrected from 50 patients who were performed tumor resection before and after 1st line chemotherapy. ABCB1 expressions were analyzed by immunohistochemical staining and the ratio of ABCB1 positive (+) vessels in total vessels were quantified. In vitro assays were performed to address how endothelial cells (ECs) are affected by change of tumor microenvironment during chemotherapy. Results: The ABCB1 (+) vessels were 0.00 – 16.80% (Median 0.00%) and 0.00-58.94% (Median 4.49%), before and after chemotherapy, respectively. In 32 of 50 cases (64%), the ratio of ABCB1 (+) vessels increased after 1st line chemotherapy. Additionally, gemcitabine induced MDR1 mRNA expression in ECs via NF-kB activation. Furthermore, gemcitabine and cisplatin induced IL-8 secretion from tumor cells, and MDR1 mRNA expression level was elevated in ECs. Conclusions: It was suggested that conventional chemotherapy may cause inflammatory change in tumor tissues, which causes in ABC transporter induction in tumor blood vessels. It was suggested that inhibition of ABC transporter in TECs is one of important new strategy to overcome cancer drug resistance.

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 Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Han-Chung Wu ◽  
De-Kuan Chang
Keyword(s):  
Drug Delivery ◽  
Endothelial Cells ◽  
Blood Vessels ◽  
Antiangiogenic Therapy ◽  
Anticancer Therapy ◽  
Liposomal Drug ◽  
Surface Receptors ◽  
Low Toxicity ◽  
Tumor Blood Vessels ◽  
Potential Methods

Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

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 VEGFR-2 Expression in Glioblastoma Multiforme Depends on Inflammatory Tumor Microenvironment

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Jana Jaal ◽  
Marju Kase ◽  
Ave Minajeva ◽  
Mikk Saretok ◽  
Aidi Adamson ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Tumor Microenvironment ◽  
Blood Vessels ◽  
Optical Density ◽  
Antiangiogenic Therapy ◽  
Growth Factor Receptor ◽  
Positive Association ◽  
Staining Intensity ◽  
Tissue Expression ◽  
The Impact

Glioblastoma multiforme (GBM) is one of the most angiogenic tumors. However, antiangiogenic therapy has not shown significant clinical efficacy. The aim of our study was to evaluate the impact of inflammatory tumor microenvironment on the expression of vascular endothelial growth factor receptor 2 (VEGFR-2). Surgically excised primary GBM tissues were histologically examined for overall extent of inflammation (score 1–3). After immunohistochemistry, the tissue expression of ICAM-1 (optical density), the number of VEGFR-2 positive (VEGFR-2+) blood vessels (per microscopic field), and the endothelial staining intensity of VEGFR-2 (score 0–3) were determined. In GBM, the extent of inflammation was 1.9 ± 0.7 (group mean ± SD). Mean optical density of inflammatory mediator ICAM-1 was 57.0 ± 27.1 (pixel values). The number of VEGFR-2+ blood vessels and endothelial VEGFR-2 staining intensity were 6.2 ± 2.4 and 1.2 ± 0.8, respectively. A positive association was found between endothelial VEGFR-2 staining intensity and the extent of inflammation (p=0.005). Moreover, VEGFR-2 staining intensity correlated with the expression level of ICAM-1 (p=0.026). The expression of VEGFR-2, one of the main targets of antiangiogenic therapy, depends on GBM microenvironment. Higher endothelial VEGFR-2 levels were seen in the presence of more pronounced inflammation. Target dependence on inflammatory tumor microenvironment has to be taken into consideration when treatment approaches that block VEGFR-2 signaling are designed.

Antiangiogenic Therapy Decreases Integrin Expression in Normalized Tumor Blood Vessels

2006 ◽  
Vol 66 (5) ◽  
pp. 2639-2649 ◽  
Author(s):  
Virginia J. Yao ◽  
Michael G. Ozawa ◽  
Amanda S. Varner ◽  
Ian M. Kasman ◽  
Yvan H. Chanthery ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Antiangiogenic Therapy ◽  
Integrin Expression ◽  
Tumor Blood Vessels

scholarly journals Potential Strategies to Improve the Effectiveness of Drug Therapy by Changing Factors Related to Tumor Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Dehong Cao ◽  
Xiaokaiti Naiyila ◽  
Jinze Li ◽  
Yin Huang ◽  
Zeyu Chen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Drug Therapy ◽  
Tumor Microenvironment ◽  
Blood Vessels ◽  
Tumor Cells ◽  
Significant Role ◽  
Cell Types ◽  
Related Factors ◽  
Continuous Interaction ◽  
Cellular Components

A tumor microenvironment (TME) is composed of various cell types and extracellular components. It contains tumor cells and is nourished by a network of blood vessels. The TME not only plays a significant role in the occurrence, development, and metastasis of tumors but also has a far-reaching impact on the effect of therapeutics. Continuous interaction between tumor cells and the environment, which is mediated by their environment, may lead to drug resistance. In this review, we focus on the key cellular components of the TME and the potential strategies to improve the effectiveness of drug therapy by changing their related factors.

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