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Review
. 2020 May 3;21(9):3238.
doi: 10.3390/ijms21093238.

Tumor Endothelial Cell-A Biological Tool for Translational Cancer Research

Dorcas Akuba-Muhyia Annan  1 , Hiroshi Kikuchi  2 , Nako Maishi  1 , Yasuhiro Hida  3 , Kyoko Hida  1
Affiliations
Review

Tumor Endothelial Cell-A Biological Tool for Translational Cancer Research

Dorcas Akuba-Muhyia Annan et al. Int J Mol Sci. .

Abstract

Going from bench to bedside is a simplified description of translational research, with the ultimate goal being to improve the health status of mankind. Tumor endothelial cells (TECs) perform angiogenesis to support the growth, establishment, and dissemination of tumors to distant organs. TECs have various features that distinguish them from normal endothelial cells, which include alterations in gene expression patterns, higher angiogenic and metabolic activities, and drug resistance tendencies. The special characteristics of TECs enhance the vulnerability of tumor blood vessels toward antiangiogenic therapeutic strategies. Therefore, apart from being a viable therapeutic target, TECs would act as a better mediator between the bench (i.e., angiogenesis research) and the bedside (i.e., clinical application of drugs discovered through research). Exploitation of TEC characteristics could reveal unidentified strategies of enhancing and monitoring antiangiogenic therapy in the treatment of cancer, which are discussed in this review.

Keywords: antiangiogenesis drugs; translational research; tumor endothelial cell.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Benefits and side effects of antiangiogenic drugs. AADs, antiangiogenesis drugs. The dependency of tumors on their resident blood vessels to grow and metastasize has led to the targeting of tumor blood vessels to starve the tumor cells and close the metastasis portals. (A) Before the administration of AADs, the tumor histology is characterized by a high density of microvessels, with an undefined order of organization. The microenvironment is generally acidic, with high lactate levels, and immunologically suppressed. (B) However, after AAD therapy, tumor blood vessels become normalized, microvessel number reduces, tumor growth recedes, and immune cells infiltrate the tumors more through the normalized vasculature. (C) In addition to these benefits, AAD use causes some undesirable effects, including tumor hypoxia (from prolonged use of AADs) and destruction of normal vessels leading to bleeding. Patients may also experience hypertension and proteinuria, among others.
Figure 2
Figure 2
TEC characteristics identified to date. Various characteristics of TECs have been observed, which make them unique when compared with endothelial cells in normal blood vessels. These range from the genetic composition and expression of genes, abnormal karyotype, higher biological activities (proliferation and motility), and TEC influence on tumor cells to modulate cancer cell metastasis and survival to modifications in their metabolic signature. TECs are not normal and their abnormality creates a targetable avenue to influence the growth of tumors and improve therapeutics in cancer treatment. TEC, tumor endothelial cells
Figure 3
Figure 3
TEC characteristics as a tool to bridge the gap between basic and clinical research in the field of tumor angiogenesis. TEC characteristics as explored in basic research are ideal targets for the development of drugs for clinical applications. Drugs that specifically target TEC characteristics can enhance vessel normalization to allow for better delivery of nanodrugs. Clinical outcomes can be noninvasively evaluated in serum by measuring TEC-secreted factors and characteristics of circulating TECs released from tumors. TEC, tumor endothelial cell; NEC, normal endothelial cell; CEC, circulating endothelial cell; AADs, antiangiogenesis drugs; TEMs, tumor endothelial markers; AATs, antiangiogenic therapies
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