Tumor Endothelial Markers Define Novel Subsets of Cancer-Specific Circulating Endothelial Cells Associated with Antitumor Efficacy
Autor: | Bernhard Riedel, Robert Schier, Zhiqiang Du, Amado J. Zurita, Monique B. Nilsson, John V. Heymach, Andrea Cortes, Reza J. Mehran, Mehrdad Khajavi, Randa El-Zein, Li Xu, Hua Kang Wu, Tina Cascone |
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Rok vydání: | 2014 |
Předmět: |
Cancer Research
Pathology medicine.medical_specialty Lung Neoplasms Mice Nude Adenocarcinoma of Lung Adenocarcinoma Biology Article Carcinoma Lewis Lung Mice Antigen Cell Line Tumor Biomarkers Tumor medicine Animals Humans In patient Progenitor cell Neovascularization Pathologic Endothelial Cells Cancer Esophageal cancer Flow Cytometry Neoplastic Cells Circulating medicine.disease Mice Inbred C57BL medicine.anatomical_structure Oncology cardiovascular system Heterografts Biomarker (medicine) Bone marrow Antiangiogenic drug Neoplasm Transplantation |
Zdroj: | Cancer Research. 74:2731-2741 |
ISSN: | 1538-7445 0008-5472 |
Popis: | 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. Cancer Res; 74(10); 2731–41. ©2014 AACR. |
Databáze: | OpenAIRE |
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