title: Tumor endothelial markers define novel subsets of cancer-specific circulating endothelial cells associated with antitumor efficacy.
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.
authors.affiliation: Authors' Affiliations: Departments of Thoracic and Cardiovascular Surgery,Thoracic/Head and Neck Medical Oncology, Epidemiology, Genitourinary Medical Oncology, and The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany; and Department of Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Reza
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Authors' Affiliations: Departments of Thoracic and Cardiovascular Surgery,Thoracic/Head and Neck Medical Oncology, Epidemiology, Genitourinary Medical Oncology, and The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany; and Department of Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Monique
authors.initials: M
authors.lastname: Nilsson
authors.affiliation: Authors' Affiliations: Departments of Thoracic and Cardiovascular Surgery,Thoracic/Head and Neck Medical Oncology, Epidemiology, Genitourinary Medical Oncology, and The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany; and Department of Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Khajavi
authors.affiliation: Authors' Affiliations: Departments of Thoracic and Cardiovascular Surgery,Thoracic/Head and Neck Medical Oncology, Epidemiology, Genitourinary Medical Oncology, and The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany; and Department of Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Du
authors.affiliation: Authors' Affiliations: Departments of Thoracic and Cardiovascular Surgery,Thoracic/Head and Neck Medical Oncology, Epidemiology, Genitourinary Medical Oncology, and The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany; and Department of Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Tina
authors.initials: T
authors.lastname: Cascone
authors.affiliation: Authors' Affiliations: Departments of Thoracic and Cardiovascular Surgery,Thoracic/Head and Neck Medical Oncology, Epidemiology, Genitourinary Medical Oncology, and The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany; and Department of Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Hua Kang
authors.initials: HK
authors.lastname: Wu
authors.affiliation: Authors' Affiliations: Departments of Thoracic and Cardiovascular Surgery,Thoracic/Head and Neck Medical Oncology, Epidemiology, Genitourinary Medical Oncology, and The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany; and Department of Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cortes
authors.affiliation: Authors' Affiliations: Departments of Thoracic and Cardiovascular Surgery,Thoracic/Head and Neck Medical Oncology, Epidemiology, Genitourinary Medical Oncology, and The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany; and Department of Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Authors' Affiliations: Departments of Thoracic and Cardiovascular Surgery,Thoracic/Head and Neck Medical Oncology, Epidemiology, Genitourinary Medical Oncology, and The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany; and Department of Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Amado
authors.initials: A
authors.lastname: Zurita
authors.affiliation: Authors' Affiliations: Departments of Thoracic and Cardiovascular Surgery,Thoracic/Head and Neck Medical Oncology, Epidemiology, Genitourinary Medical Oncology, and The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany; and Department of Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Schier
authors.affiliation: Authors' Affiliations: Departments of Thoracic and Cardiovascular Surgery,Thoracic/Head and Neck Medical Oncology, Epidemiology, Genitourinary Medical Oncology, and The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany; and Department of Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Riedel
authors.affiliation: Authors' Affiliations: Departments of Thoracic and Cardiovascular Surgery,Thoracic/Head and Neck Medical Oncology, Epidemiology, Genitourinary Medical Oncology, and The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany; and Department of Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Randa
authors.initials: R
authors.lastname: El-Zein
authors.affiliation: Authors' Affiliations: Departments of Thoracic and Cardiovascular Surgery,Thoracic/Head and Neck Medical Oncology, Epidemiology, Genitourinary Medical Oncology, and The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany; and Department of Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria, Australia jheymach@mdanderson.org.
authors.forename: John V
authors.initials: JV
authors.lastname: Heymach
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000098:blood supply / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D018827:Carcinoma, Lewis Lung / Q000097:blood / Q000098:blood supply / Q000473:pathology; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000473:pathology*; D005434:Flow Cytometry; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000098:blood supply / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000097:blood / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor