Angiogenesis and Ovarian Cancer: What Potential Do Different Subtypes of Circulating Endothelial Cells Have for Clinical Application?

Abstract

Ovarian cancer (OC) remains the most fatal disease of gynaecologic malignant tumours. The neovasculature in the tumour microenvironment principally comprises endothelial cells. Haematogenous cancer metastases are significantly impacted by tumour neovascularisation, which predominantly depends on the tumour-derived endothelial vasculogenesis. There is an urgent need for biomarkers for the diagnosis, prognosis and prediction of drug response. Endothelial cells play a key role in angiogenesis and other forms of tumour vascularisation. Subtypes of circulating endothelial cells may provide interesting non-invasive biomarkers of advanced OC that might have the potential to be included in clinical analysis for patients' stratification and therapeutic management. In this review, we summarise the reported studies on circulating endothelial subtypes in OC, detailing their isolation methods as well as their potential diagnostic, prognostic, predictive and therapeutic utility for clinical application. We highlight key biomarkers for the identification of circulating endothelial cell subtypes and their targets for therapies and critically point out future challenges.

Keywords: CECs; CEPCs; CTECs; angiogenesis; circulating endothelial cells; circulating endothelial progenitor cells; circulating tumour endothelial cells; ovarian cancer.

Figure 1

Schematic representation of the different neovascularisation processes: angiogenesis (up panel), vasculogenesis (mid-panel), and vasculogenic mimicry (low panel). Image created with biorender.

Figure 2

Schematic representation of circulating endothelial cells isolation and detection workflow. Abbreviations: CECs: circulating endothelial cells; CEPCs: circulating endothelial progenitor cells; CTECs: circulating tumour endothelial cells; ECs: endothelial cells; RBCs: red blood cells. Image created with biorender.

Figure 3

Graphical summary of the main biomarkers for the detection of CEC subtypes (detection biomarker boxes), the CEC subtypes-associated biomarkers with therapeutic potential (markers with therapeutic potential boxes) and the main clinical findings regarding the levels of CEC subtypes in OC (clinical relevance boxes). The plus symbol (+) indicates the expression of the corresponding biomarker in reference cells. Abbreviations: ND: not determined; OS: overall survival. Image created with biorender.