Tumor-derived circulating endothelial cell clusters in colorectal cancer.

Handle URI:
http://hdl.handle.net/10754/615874
Title:
Tumor-derived circulating endothelial cell clusters in colorectal cancer.
Authors:
Cima, Igor; Kong, Say Li; Sengupta, Debarka; Tan, Iain B; Phyo, Wai Min; Lee, Daniel; Hu, Min; Iliescu, Ciprian; Alexander, Irina; Goh, Wei Lin; Rahmani, Mehran; Suhaimi, Nur-Afidah Mohamed; Vo, Jess H; Tai, Joyce A; Tan, Joanna H; Chua, Clarinda; Ten, Rachel; Lim, Wan Jun; Chew, Min Hoe; Hauser, Charlotte ( 0000-0001-8251-7246 ) ; van Dam, Rob M; Lim, Wei-Yen; Prabhakar, Shyam; Lim, Bing; Koh, Poh Koon; Robson, Paul; Ying, Jackie Y; Hillmer, Axel M; Tan, Min-Han
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.
KAUST Department:
Biological and Environmental Sciences & Engineering Division
Citation:
Tumor-derived circulating endothelial cell clusters in colorectal cancer. 2016, 8 (345):345ra89 Sci Transl Med
Publisher:
American Association for the Advancement of Science (AAAS)
Journal:
Science Translational Medicine
Issue Date:
29-Jun-2016
DOI:
10.1126/scitranslmed.aad7369
PubMed ID:
27358499
Type:
Article
ISSN:
1946-6242
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorCima, Igoren
dc.contributor.authorKong, Say Lien
dc.contributor.authorSengupta, Debarkaen
dc.contributor.authorTan, Iain Ben
dc.contributor.authorPhyo, Wai Minen
dc.contributor.authorLee, Danielen
dc.contributor.authorHu, Minen
dc.contributor.authorIliescu, Ciprianen
dc.contributor.authorAlexander, Irinaen
dc.contributor.authorGoh, Wei Linen
dc.contributor.authorRahmani, Mehranen
dc.contributor.authorSuhaimi, Nur-Afidah Mohameden
dc.contributor.authorVo, Jess Hen
dc.contributor.authorTai, Joyce Aen
dc.contributor.authorTan, Joanna Hen
dc.contributor.authorChua, Clarindaen
dc.contributor.authorTen, Rachelen
dc.contributor.authorLim, Wan Junen
dc.contributor.authorChew, Min Hoeen
dc.contributor.authorHauser, Charlotteen
dc.contributor.authorvan Dam, Rob Men
dc.contributor.authorLim, Wei-Yenen
dc.contributor.authorPrabhakar, Shyamen
dc.contributor.authorLim, Bingen
dc.contributor.authorKoh, Poh Koonen
dc.contributor.authorRobson, Paulen
dc.contributor.authorYing, Jackie Yen
dc.contributor.authorHillmer, Axel Men
dc.contributor.authorTan, Min-Hanen
dc.date.accessioned2016-07-10T08:04:32Z-
dc.date.available2016-07-10T08:04:32Z-
dc.date.issued2016-06-29-
dc.identifier.citationTumor-derived circulating endothelial cell clusters in colorectal cancer. 2016, 8 (345):345ra89 Sci Transl Meden
dc.identifier.issn1946-6242-
dc.identifier.pmid27358499-
dc.identifier.doi10.1126/scitranslmed.aad7369-
dc.identifier.urihttp://hdl.handle.net/10754/615874-
dc.description.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.en
dc.language.isoenen
dc.language.isoen-
dc.publisherAmerican Association for the Advancement of Science (AAAS)en
dc.rightsArchived with thanks to Science translational medicineen
dc.subjectColorectal canceren
dc.subjectEndothelial cellsen
dc.subjectTumor cellsen
dc.subjectBiomarkeren
dc.subjectCirculating Tumor Cellsen
dc.subjectSingle cell analysisen
dc.titleTumor-derived circulating endothelial cell clusters in colorectal cancer.en
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences & Engineering Divisionen
dc.identifier.journalScience Translational Medicineen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionInstitute of Bioengineering and Nanotechnology, Singapore 138669, Singaporeen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorCima, Igoren
kaust.authorAlexander, Irinaen
kaust.authorHauser, Charlotteen

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