Tumor-derived circulating endothelial cell clusters in colorectal cancer

Circulating tumor cells (CTCs) are the subject of several translational studies and clinical trials because their examination could offer an insight into tumor progression and clinical outcomes. Circulating tumor microemboli (CTM) are clusters of CTCs that have been described as malignant entities for over 50 years, although a comprehensive characterization of these cells is still lacking. Contrary to current consensus, we demonstrate that CTM isolated from colorectal cancer patients are not cancerous, but represent a discrete population of tumor-derived endothelial cells. CTM express epithelial and mesenchymal markers that are consistent with previous reports on circulating tumor cell phenotyping. However, they do not mirror the genetic variations of matching tumors. Transcriptome analysis of single-CTM reveals that these structures exhibit an endothelial phenotype, with further results supporting a tumor-derived endothelial lineage. CTM are widespread in blood sampled from preoperative cancer patients but not in healthy donors, suggesting CTM count as a potential biomarker of interest for colorectal cancer. CTM should not be confused with bona fide circulating epithelial tumor cells. The characterization of tumor derived endothelial cell clusters (TECCs) is likely of high diagnostic value, and may provide direct information about the underlying tumor vasculature at the time of diagnosis, during treatment and the course of the disease. Overall design: Profiling of 18 TECCs/CTM from 8 colorectal cancer patients. In addition profiling of matched 7 normal colonic mucosa, 9 primary colorectal tumor samples (of which three from the same patient), one colorectal cancer metastatis. Additionally, 14 laser-capture-dissected endothelia from the same patients and tissues, and 3 commercially available normal endothelial cell lines

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Cima I, Kong SL, Sengupta D, Tan IB, Phyo WM, Lee D, Hu M, Iliescu C, Alexander I, Goh WL, Rahmani M, Suhaimi NA, Vo JH, Tai JA, Tan JH, Chua C, Ten R, Lim WJ, Chew MH, Hauser CA, van Dam RM, Lim WY, Prabhakar S, Lim B, Koh PK, Robson P, Ying JY, Hillmer AM, Tan MH