Circulating tumor cells (CTCs) in the blood of cancer patients have attracted intense scrutiny because of the potential they offer as easily accessible biomarkers and indicators of therapeutic response. In addition to circulating as individual cells, CTCs have long been observed as multiple-cell clusters. Unfortunately, characterizing the clusters has been limited by technical challenges, so while they were thought to be malignant, their actual clinical relevance has not been well-defined.
A research team including Paul Robson, Ph.D., director of single-cell biology at JAX, used recent advances in microfiltration, high-throughput sequencing and single-cell genomics to comprehensively study circulating clusters of cells in cancer patients. They obtained the cells from a cohort of colorectal cancer patients as well as healthy volunteers, and found that the cluster of cells from the patients were not malignant and, surprisingly, were not epithelial but in fact endothelial cells. These cells did not contain mutations found in the corresponding tumors, but contained specific markers indicative of tumor vascular endothelial cells.
Additional functional analysis confirmed that these tumor-derived clusters likely come from tumor endothelium, and the researchers hypothesize that they are shed from the tumor vasculature. Essentially, the active, sometimes chaotic blood vessel growth in the tumor produces the cell clusters, although it’s unclear how they get from the tumor to the peripheral blood vasculature. And they can indicate early-stage colorectal cancer. At least one cluster was detected in 86.5% (45/52) of the samples obtained from yet-to-be treated patients, while they were found in only 2.2% (1/45) of healthy subjects. The results indicate that the presence of endothelial cell clusters could be a useful diagnostic for colorectal cancer, even in early stages of disease, despite their distinct differences from circulating cancerous cells derived from the primary tumor epithelium, which are implicated as the conduit of cancer metastasis..
Tumor-derived circulating endothelial cell clusters in colorectal cancer. Science Translational Medicine. 29 Jun 2016: Vol. 8, Issue 345, pp. 345ra89 DOI: 10.1126/scitranslmed.aad7369