Circulating Endothelial Cells and Their Subsets: Novel Biomarkers for Cancer

Abstract

Angiogenesis contributes to the growth of solid tumors. Antiangiogenic agents are widely used in various cancers and considerable efforts have been made in the development of novel biomarkers that can predict the outcome of an anticancer treatment. Of those, circulating endothelial cells (CECs) and their subsets constitute a surrogate tool for monitoring disease activity. However, owing to the lack of standardization on the phenotypes and detection of CECs and their subsets, results have always been inconsistent and uninterpretable. In this review, we focus on the biological characteristics in terms of physiology, phenotypes and detection of CECs along with their subsets; review the current scenario of CEC enumeration as a surrogate biomarker in clinical oncology; and explore their future potential applications.

ctDNA and CTCs in Liquid Biopsy – Current Status and Where We Need to Progress

“…Rare cells are generally considered low abundant cells in the blood stream, typically with a concentration below 1 in 10 5 cells. Circulating mature endothelial cells (CECs), which are potential biomarkers for endothelial dysfunction in cancer, diabetes, cardio-vascular or acute kidney diseases [ [16] , [17] , [18] ] have been observed with a frequency of 10–100 CECs in 10 6 –10 8 white blood cells, depending on the method of enrichment and detection. Compared to that, the estimated frequency of CTCs is even lower, ranging from 1 to 10 CTCs in 10 6 –10 8 white blood cells.…”

Predicting the response to neoadjuvant therapy for early-stage breast cancer: tumor-, blood-, and imaging-related biomarkers

“… 34 They might be useful for diagnosis, prognosis, and real-time therapy monitoring with lower costs and higher compliance than tumor biopsy, due to their minimal invasiveness. 34 This section addresses circulating tumor cells (CTCs), 35 circulating endothelial cells (CECs), 36 and the circulating tumor DNA (ctDNA), which are rare populations in the peripheral circulation and potential biomarkers. Although myeloid-derived suppressor cells (MDSCs) and various lymphocyte subpopulations are also present in the peripheral blood, they are discussed in the “Immunological biomarkers” section.…”

“…Endothelial cells can enter circulation as CECs when sloughing off vessel walls and as endothelial progenitor cells (EPCs) when mobilized from the bone marrow. 36 Both CECs and their populations, which can be enumerated by flow cytomery, 56 – 58 could potentially serve as biomarkers for the prognosis and prediction of various solid tumors. 36 CECs and EPCs appear to change dynamically during the course of chemotherapy of patients with breast cancer.…”

“… 36 Both CECs and their populations, which can be enumerated by flow cytomery, 56 – 58 could potentially serve as biomarkers for the prognosis and prediction of various solid tumors. 36 CECs and EPCs appear to change dynamically during the course of chemotherapy of patients with breast cancer. A decrease in CECs and an increase in EPCs could serve as surrogate markers of angiogenesis in antiangiogenesis treatments combined with chemotherapy.…”

Optimized multiparametric flow cytometric analysis of circulating endothelial cells and their subpopulations in peripheral blood of patients with solid tumors: a technical analysis

“…These CEC subpopulations include mature CECs (mCECs), resting and activated CECs (rCECs and aCECs, respectively), and endothelial progenitor cells (EPCs). 9 CECs contribute to angiogenesis, and increased CEC levels have been reported in patients with various malignancies. Kraan et al reviewed the potential clinical applications of CECs in cancer treatment.…”