Identification and Clinical Significance of Circulating Endothelial Progenitor Cells in Human Non–Small Cell Lung Cancer

Abstract

Until recently, it was generally accepted that vascularization of tumors arises exclusively from endothelial sprouting. Whether circulating bone marrow-derived endothelial progenitor cells (EPC) participate in the progression of non-small cell lung cancer (NSCLC) has not yet been evaluated. EPCs labeled with CD34, CD133, and vascular endothelial growth factor receptor-2 (VEGFR2) antibodies were counted by flow cytometry in the peripheral blood of 53 NSCLC patients. Furthermore, by means of a quantitative reverse transcription-PCR approach, we measured VEGFR2, CD133, CD34, and VE-cadherin mRNA in the peripheral blood samples of the same patient population. EPCs in tumor samples were identified by confocal microscopy using CD31, CD34, CD133, and VEGFR2 antibodies. Although immunofluorescent labeling of microvessels made clear that incorporation of EPCs is a rare phenomenon in NSCLC tissue (9 of 22 cases), circulating EPC levels before therapeutic intervention were increased in NSCLC patients (P < 0.002, versus healthy controls), and high pretreatment circulating EPC numbers correlated with poor overall survival (P < 0.001). Furthermore, in the subgroup of responders to treatment, the posttreatment EPC numbers in the peripheral blood were significantly lower compared with nonresponding patients. Interestingly, pretreatment mRNA levels of CD133, VE-cadherin, and CD34 were not significantly increased in NSCLC patients, whereas VEGFR2 expression was increased by 80-fold. Moreover, posttreatment VEGFR2 mRNA level in the peripheral blood was significantly higher in the subgroup of nonresponding patients when compared with posttreatment level of patients responding to antitumor therapy. Circulating levels of bone marrow-derived EPCs are significantly increased in NSCLC patients and correlate with clinical behavior. (Cancer Res 2006; 66(14): 7341-7)

Circulating endothelial cells in patients with chronic lymphocytic leukemia

“…It is noteworthy that several reports have suggested that CECs and EPCs are increased in patients with cancer and are correlated with a more aggressive disease course. [2][3][4] Overall, these findings suggest that CECs may be related to the so-called angiogenic switch, a phenomenon that characterizes the shift to a more aggressive course of the disease, and support the idea that, in CLL, CECs may represent a new and easy-to-use prognostic marker to be tested in large multicenter series of patients for correlation with prognosis. It remains to be determined whether, in patients with CLL, CECs can be used as a surrogate marker to monitor the efficacy of therapy and whether patients with high CEC levels may represent a subset of patients who are eligible for antiangiogenic treatments, including new drugs like lenalidomide.…”

IL-17A, But Not IL-17F, Is Indispensable for Airway Vascular Remodeling Induced by Exaggerated Th17 Cell Responses in Prolonged Ovalbumin-Challenged Mice

“…In addition, analysis of the relation between IL-17A and MVD in Accumulating evidence has revealed that bone marrow-derived EPCs are involved in the process of vasculogenesis in physiological or pathological neovascularization. Dome et al (25) found that the levels of bone marrow-derived EPCs significantly increased in patients with non-small-cell lung cancer and were arrested in small intratumoral capillaries or located in the capillary walls. Asosingh et al (18) demonstrated that circulating EPCs were increased in asthma patients and were related to the increased numbers of submucosal vessels.…”

Endothelial progenitor cells for cancer gene therapy

“…In cancer patients, the number of circulating EPCs is increased. [12][13][14] Importantly, in various animal tumor models, transplanted EPCs incorporated functionally into tumor-associated vessels. Following transplantation of marked bone marrow into tumorbearing mice, marked cells were found in the neovasculature of the developing tumors.…”