Busting Myths on Tumor Cell Clusters

A surprising finding shows that some clusters of cells commonly found in the bloodstream of colorectal cancer patients are actually non-cancerous

tumor cell
Clusters of human cells originating from blood vessels captured from the bloodstream by using a custom-designed microdevice. © 2016 A*STAR Institute of Bioengineering and Nanotechnology

In a major debunking of scientific orthodoxy, A*STAR researchers have discovered a new type of tumor-derived cells that are non-cancerous floating in the bloodstream1. This finding promises to open novel, non-invasive ways to detect and monitor the spread of cancer in the body.

For decades, clusters of cells circulating in the bloodstream of cancer patients have been regarded as invasive cancerous cells shed by the tumor. They have been implicated in spreading cancer to other parts of the body, resulting in secondary tumors that are often harder to kill than the initial tumor.

Now, Min-Han Tan of the A*STAR Institute of Bioengineering and Nanotechnology (IBN) and his co-workers have exonerated some clusters of circulating tumor cells, finding that they are not actually cancerous.

The discovery goes against half a century of received wisdom that all varieties of circulating tumor cells are malignant. “This was an absolutely surprising result,” comments Tan. “When we first set out on this study, we expected to find that these clusters were cancerous.”

The researchers used a custom-designed microdevice, which was developed by Jackie Y. Ying’s team at IBN, to trap cell clusters in blood samples of 80 patients with colorectal cancer (see image). Analysis of the cells’ DNA and RNA revealed that the cells originated from the innermost lining of blood vessels that line the tumor, rather than from the tumor itself. Tan and the team also found that these clusters detached intact from blood vessels near a tumor and were not formed by individual cells coming together in the bloodstream.

By monitoring these clusters, doctors should be able to glean vital information about cancer in other parts of the body during the course of treatment. “What I think excites everyone is the chance to measure the vascular health of a tumor non-invasively, which has never hitherto been possible,” explains Tan. “One can imagine administering drugs and evaluating the impact of such agents on the tumor vasculature.”

It may even be possible to use the clusters to diagnose certain cancers. “Unexpectedly, we found that these clusters commonly occur even in the early stage of colorectal cancer, which opens up an opportunity to investigate using these cell clusters for cancer screening,” adds Tan.

In the future, the team intends to study these circulating cell clusters in other types of cancers. They also plan to develop improved ways to capture and characterize these clusters.