Tumor-derived circulating endothelial cell clusters in colorectal cancer.
Kong, Say Li
Tan, Iain B
Phyo, Wai Min
Goh, Wei Lin
Suhaimi, Nur-Afidah Mohamed
Vo, Jess H
Tai, Joyce A
Tan, Joanna H
Lim, Wan Jun
Chew, Min Hoe
van Dam, Rob M
Koh, Poh Koon
Ying, Jackie Y
Hillmer, Axel M
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Computational Bioscience Research Center (CBRC)
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Biological and Environmental Sciences & Engineering Division
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AbstractClusters 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.
CitationTumor-derived circulating endothelial cell clusters in colorectal cancer. 2016, 8 (345):345ra89 Sci Transl Med
JournalScience Translational Medicine
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