Circulating endothelial cells in oncology: pitfalls and promises

Abstract

Adequate blood supply is a prerequisite in the pathogenesis of solid malignancies. As a result, depriving a tumour from its oxygen and nutrients, either by preventing the formation of new vessels, or by disrupting vessels already present in the tumour, appears to be an effective treatment modality in oncology. Given the mechanism by which these agents exert their anti-tumour activity together with the crucial role of tumour vasculature in the pathogenesis of tumours, there is a great need for markers properly reflecting its impact. Circulating endothelial cells (CEC), which are thought to derive from damaged vasculature, may be such a marker. Appropriate enumeration of these cells appears to be a technical challenge. Nevertheless, first studies using validated CEC assays have shown that CEC numbers in patients with advanced malignancies are elevated compared to healthy controls making CEC a potential tool for among other establishing prognosis and therapy-induced effects. In this review, we will address the possible clinical applications of CEC detection in oncology, as well as the pitfalls encountered in this process.

Antiangiogenic drugs in ovarian cancer

“…A subsequent study by the same group has suggested that an elevated CEC level before treatment commencement predicted clinical benefit from the combination of metronomic chemotherapy and bevacizumab in metastatic breast cancer (Dellapasqua et al, 2008). However, although these results are intriguing, it should be noted that the appropriate enumeration of CECs is technically challenging (Strijbos et al, 2008). Interestingly, comparative data from four phase II clinical trials of anti-VEGF agents presented at ASCO this year in which an identical technology was used to measure CECs indicated that changes in CEC/CEP levels did not demonstrate a consistent pattern but were dependent on the antiangiogenic agent used and the treatment context (Duda et al, 2008).…”

Detection of circulating tumor cells in breast cancer may improve through enrichment with anti-CD146

“…Unbound cells and the remaining plasma as provided in the CellSearch Epithelial Cell kit. As CD146 enriches for circulating endothelial cells (CECs) [15], and CECs can express cytokeratin 18 [16], a marker to exclude the cytokeratin 18-expressing subset of CECs was needed. As CD34 is a pan-endothelial marker [17] …”

“…While leukocytes can be excluded with CD45, which is already incorporated in the standard CellSearch Circulating Epithelial Cell kit, we assessed whether CECs could be excluded with CD34, a pan-endothelial marker [15,17]. CD34 proved to be a suitable marker to distinguish CTCs from CECs, as none of the normal-like cell lines expressed CD34 as determined by flow cytometry (Table 1).…”

Decreased exposure to sunitinib due to concomitant administration of ifosfamide: results of a phase I and pharmacokinetic study on the combination of sunitinib and ifosfamide in patients with advanced solid malignancies

“…Alterations in CEC numbers is likely to reflect vascular damage (Strijbos et al, 2008), but no consistent changes in CEC numbers could be seen, either during therapy or between the two sunitinib doses explored. In contrast to Phase I sunitinib ifosfamide P Hamberg et al monotherapy with sunitinib (Deprimo et al, 2007), no consistent pattern in the changes in plasma concentrations of VEGF and sVEGFR2 was observed.…”