Mehran, Reza, Nilsson, Monique, Khajavi, Mehrdad, Du, Zhiqiang, Cascone, Tina, Wu, Hua Kang, Cortes, Andrea, Xu, Li, Zurita, Amado, Schier, Robert, Riedel, Bernhard, El-Zein, Randa and Heymach, John V. (2014). Tumor Endothelial Markers Define Novel Subsets of Cancer-Specific Circulating Endothelial Cells Associated with Antitumor Efficacy. Cancer Res., 74 (10). S. 2731 - 2742. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1538-7445

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Abstract

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. (C)2014 AACR.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Mehran, RezaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nilsson, MoniqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khajavi, MehrdadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Du, ZhiqiangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cascone, TinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, Hua KangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cortes, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xu, LiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zurita, AmadoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schier, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riedel, BernhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
El-Zein, RandaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heymach, John V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-438281
DOI: 10.1158/0008-5472.CAN-13-2044
Journal or Publication Title: Cancer Res.
Volume: 74
Number: 10
Page Range: S. 2731 - 2742
Date: 2014
Publisher: AMER ASSOC CANCER RESEARCH
Place of Publication: PHILADELPHIA
ISSN: 1538-7445
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HEMATOPOIETIC STEM-CELLS; PROGENITOR CELLS; SURROGATE MARKER; METRONOMIC CHEMOTHERAPY; INDUCED MOBILIZATION; IN-VIVO; GROWTH; ANGIOGENESIS; BEVACIZUMAB; RECRUITMENTMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/43828

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