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Sci Transl Med. 2016 Jun 29;8(345):345ra89. doi: 10.1126/scitranslmed.aad7369.

Tumor-derived circulating endothelial cell clusters in colorectal cancer.

Author information

1
Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore. Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
2
Genome Institute of Singapore, Singapore 138672, Singapore.
3
Genome Institute of Singapore, Singapore 138672, Singapore. National Cancer Centre Singapore, Singapore 169610, Singapore.
4
Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
5
Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia. IFOM-p53Lab Joint Research Laboratory, Singapore 138648, Singapore.
6
Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore. Fortis Surgical Hospital, Singapore 289891, Singapore.
7
National Cancer Centre Singapore, Singapore 169610, Singapore.
8
Singapore General Hospital, Singapore 169608, Singapore.
9
Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
10
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117549, Singapore.
11
Genome Institute of Singapore, Singapore 138672, Singapore. The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
12
Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore. National Cancer Centre Singapore, Singapore 169610, Singapore. Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117549, Singapore. Concord Cancer Hospital, Singapore 289891, Singapore. mhtan@ibn.a-star.edu.sg.

Abstract

Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumor-derived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease.

PMID:
27358499
DOI:
10.1126/scitranslmed.aad7369
[Indexed for MEDLINE]

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