The multifaceted circulating endothelial cell in cancer: towards marker and target identification

Key Points Circulating endothelial cells (CECs) with a mature phenotype, which are probably derived from blood vessel wall turnover, are increased in patients with some types of cancer and in various other conditions including mechanical, inflammatory, infective, ischaemic and autoimmune states. A subpopulation of CECs shows a progenitor-like phenotype. Preclinical and clinical data indicate that these circulating endothelial progenitors (CEPs) can incorporate in cancer vessels, albeit usually at low frequencies. Some preclinical studies suggest that CEPs have a key role in promoting cancer vasculogenesis and in late stages of cancer development. Therefore, CEP-targeting drugs (including many anti-angiogenic agents) might, in principle, inhibit cancer growth. CEC and CEP numbers, kinetics and viability can be measured by different approaches, including positive enrichment by immunobeads and flow cytometry. However, so far no single antigen has been successfully exploited to discriminate between endothelial and haematopoietic cells; consequently, a multiparametric investigation at the single-cell level is mandatory at present. CEC measurement has been found to correlate well with well-known preclinical assays of angiogenesis, such as the corneal micropocket assay, which cannot be adapted for use in patients. In addition, CEC kinetics and viability have been found to correlate with clinical outcomes in cancer patients treated with anti-angiogenic therapeutic approaches. CECs and/or CEPs might, in the future, be used to deliver drugs to cancer vessels. The number of circulating endothelial cells and their progenitors is increased in some types of cancer, and there is evidence that aspects of these cells might correlate with clinical outcome of cancer patients treated with anti-angiogenic drugs. Increases in the number of circulating endothelial cells (CECs) and progenitors (CEPs) have been reported in various pathological conditions including cancer. Preclinical studies have shown that CEC and CEP kinetics correlate well with several standard laboratory angiogenesis assays, which cannot be used in humans. At the clinical level, evidence is emerging that CEC kinetics and viability might correlate with clinical outcomes in cancer patients who undergo anti-angiogenic treatment. Therefore, CEC and CEP measurement has potential as a surrogate marker for monitoring anti-angiogenic treatment and drug activity, and could help to determine the optimal biological dose