title: Tumor-derived circulating endothelial cell clusters in colorectal cancer.
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.
authors.affiliation: 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.
authors.forename: Igor
authors.initials: I
authors.lastname: Cima
authors.affiliation: Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Say Li
authors.initials: SL
authors.lastname: Kong
authors.affiliation: Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Debarka
authors.initials: D
authors.lastname: Sengupta
authors.affiliation: Genome Institute of Singapore, Singapore 138672, Singapore. National Cancer Centre Singapore, Singapore 169610, Singapore.
authors.forename: Iain B
authors.initials: IB
authors.lastname: Tan
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Wai Min
authors.initials: WM
authors.lastname: Phyo
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lee
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Ciprian
authors.initials: C
authors.lastname: Iliescu
authors.affiliation: 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.
authors.forename: Irina
authors.initials: I
authors.lastname: Alexander
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore. Fortis Surgical Hospital, Singapore 289891, Singapore.
authors.forename: Wei Lin
authors.initials: WL
authors.lastname: Goh
authors.affiliation: Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Mehran
authors.initials: M
authors.lastname: Rahmani
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Nur-Afidah Mohamed
authors.initials: NA
authors.lastname: Suhaimi
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Jess H
authors.initials: JH
authors.lastname: Vo
authors.affiliation: Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Tai
authors.affiliation: Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Joanna H
authors.initials: JH
authors.lastname: Tan
authors.affiliation: National Cancer Centre Singapore, Singapore 169610, Singapore.
authors.forename: Clarinda
authors.initials: C
authors.lastname: Chua
authors.affiliation: National Cancer Centre Singapore, Singapore 169610, Singapore.
authors.forename: Rachel
authors.initials: R
authors.lastname: Ten
authors.affiliation: National Cancer Centre Singapore, Singapore 169610, Singapore.
authors.forename: Wan Jun
authors.initials: WJ
authors.lastname: Lim
authors.affiliation: Singapore General Hospital, Singapore 169608, Singapore.
authors.forename: Min Hoe
authors.initials: MH
authors.lastname: Chew
authors.affiliation: Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
authors.forename: Charlotte A E
authors.initials: CA
authors.lastname: Hauser
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117549, Singapore.
authors.forename: Rob M
authors.initials: RM
authors.lastname: van Dam
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117549, Singapore.
authors.forename: Wei-Yen
authors.initials: WY
authors.lastname: Lim
authors.affiliation: Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Shyam
authors.initials: S
authors.lastname: Prabhakar
authors.affiliation: Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Bing
authors.initials: B
authors.lastname: Lim
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore. Fortis Surgical Hospital, Singapore 289891, Singapore.
authors.forename: Poh Koon
authors.initials: PK
authors.lastname: Koh
authors.affiliation: Genome Institute of Singapore, Singapore 138672, Singapore. The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Robson
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Jackie Y
authors.initials: JY
authors.lastname: Ying
authors.affiliation: Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Axel M
authors.initials: AM
authors.lastname: Hillmer
authors.affiliation: 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.
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Tan
mesh_terms: D002460:Cell Line; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family / Q000235:genetics; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D014407:Tumor Cells, Cultured
chemical_list: D007633:Keratins; D017493:Leukocyte Common Antigens