TY - JOUR
T1 - Tumor endothelial markers define novel subsets of cancer-specific circulating endothelial cells associated with antitumor efficacy
AU - Mehran, Reza
AU - Nilsson, Monique
AU - Khajavi, Mehrdad
AU - Du, Zhiqiang
AU - Cascone, Tina
AU - Wu, Hua Kang
AU - Cortes, Andrea
AU - Xu, Li
AU - Zurita, Amado
AU - Schier, Robert
AU - Riedel, Bernhard
AU - El-Zein, Randa
AU - Heymach, John V.
PY - 2014/5/15
Y1 - 2014/5/15
N2 - Circulating endothelial cells (CEC) are derived from multiple sources, including bone marrow (circulating endothelial progenitors; CEP), and established vasculature (mature CEC). Although CECs have shown promise as a biomarker for patients with cancer, their utility has been limited, in part, by the lack of specificity for tumor vasculature and the different nonmalignant causes that can impact CEC. Tumor endothelial markers (TEM) are antigens enriched in tumor versus nonmalignant endothelia. We hypothesized that TEMs may be detectable on CEC and that these circulating TEM+ endothelial cells (CTEC) may be a more specific marker for cancer and tumor response than standard CEC. We found that tumor-bearing mice had a relative increase in numbers of circulating CTEC, specifically with increased levels of TEM7 and TEM8 expression. Following treatment with various vascular-targeting agents, we observed a decrease in CTEC that correlated with the reductions in tumor growth. We extended these findings to human clinical samples and observed that CTECs were present in patients with esophageal cancer and non-small cell lung cancer (N = 40), and their levels decreased after surgical resection. These results demonstrate that CTECs are detectable in preclinical cancer models and patients with cancer. Furthermore, they suggest that CTECs offer a novel cancer-Associated marker that may be useful as a blood-based surrogate for assessing the presence of tumor vasculature and antiangiogenic drug activity.
AB - Circulating endothelial cells (CEC) are derived from multiple sources, including bone marrow (circulating endothelial progenitors; CEP), and established vasculature (mature CEC). Although CECs have shown promise as a biomarker for patients with cancer, their utility has been limited, in part, by the lack of specificity for tumor vasculature and the different nonmalignant causes that can impact CEC. Tumor endothelial markers (TEM) are antigens enriched in tumor versus nonmalignant endothelia. We hypothesized that TEMs may be detectable on CEC and that these circulating TEM+ endothelial cells (CTEC) may be a more specific marker for cancer and tumor response than standard CEC. We found that tumor-bearing mice had a relative increase in numbers of circulating CTEC, specifically with increased levels of TEM7 and TEM8 expression. Following treatment with various vascular-targeting agents, we observed a decrease in CTEC that correlated with the reductions in tumor growth. We extended these findings to human clinical samples and observed that CTECs were present in patients with esophageal cancer and non-small cell lung cancer (N = 40), and their levels decreased after surgical resection. These results demonstrate that CTECs are detectable in preclinical cancer models and patients with cancer. Furthermore, they suggest that CTECs offer a novel cancer-Associated marker that may be useful as a blood-based surrogate for assessing the presence of tumor vasculature and antiangiogenic drug activity.
UR - http://www.scopus.com/inward/record.url?scp=84901273142&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901273142&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-13-2044
DO - 10.1158/0008-5472.CAN-13-2044
M3 - Article
C2 - 24626092
AN - SCOPUS:84901273142
SN - 0008-5472
VL - 74
SP - 2731
EP - 2741
JO - Cancer Research
JF - Cancer Research
IS - 10
ER -