Clusters of circulating cells commonly found in the blood of cancer patients have long been the subject of research on cancer. These clusters have been regarded for more than 50 years as malignant cells that have broken off from the primary tumour, spreading cancer to other parts of the body.
But researchers at the Institute of Bioengineering and Nanotechnology (IBN) of A*STAR in Singapore have reported that these clusters are unlike what has been assumed previously, potentially opening up new ways to detect and inhibit the spread of cancer.
Due to the technical challenges of separating these clusters from normal blood cells, limited research has been performed on them. The working assumption was that these cell clusters are malignant cells from the tumour.
A national research team led by Dr Min-Han Tan, Team Leader and Principal Research Scientist at IBN, has shown that these cell clusters come from the blood vessels that line the tumour rather than from the tumour itself. The team includes researchers from IBN, A*STAR's Genome Institute of Singapore, Concord Cancer Hospital, National University of Singapore, National Cancer Centre Singapore, and Singapore General Hospital.
Knowing exactly where these circulating cell clusters come from will lead us towards better approaches of diagnosing and treating cancer
The team set out to study these circulating cell clusters at a single cell-scale in 80 colorectal cancer patients. They first separated the cell clusters from the blood samples using a custom-designed microdevice developed by Prof Jackie Y. Ying's laboratory at IBN that enables quick and efficient capture and retrieval of the circulating cell clusters. They then used high-throughput DNA and RNA sequencing and computational modelling to determine the identity of these cells.
After four years of research, the results confirmed that in colorectal cancer, these circulating cell clusters are endothelial cells from the blood vessels lining the tumour and are non-cancerous. Unexpectedly, the researchers also discovered that more endothelial cell clusters were found in colorectal cancer patients who have not received any treatment, compared with those who have received treatment, suggesting that these cells could be used for early-stage cancer detection.
'The goal of cancer research is to understand how cancer spreads in order to curb the disease. Our institute has been focusing on evaluating cancer in a non-invasive way through blood testing using our novel microfiltration technique. Knowing exactly where these circulating cell clusters come from will lead us towards better approaches of diagnosing and treating cancer,' said Prof. Ying.
'Scientific orthodoxy has maintained for decades that these cell clusters commonly observed in cancer patients were malignant tumour cells. In contrast, we found that these cell clusters are not malignant, but come from the blood vessels lining the tumour that presumably peeled off during blood flow through the tumour. This insight requires a reconsideration of decades of data, and gives scientists new opportunities to investigate and starve the cancer through drugs that manipulate the blood vessels of tumours. This method also gives physicians a new understanding and method of monitoring tumour blood supply in cancer patients receiving treatment,' said Dr Min-Han Tan.
The next stage of this research is to determine if the same finding applies to other types of cancer, and to develop new liquid biopsy technologies for cancer detection and drug treatment based on these circulating cell clusters.
The research paper was recently published in the interdisciplinary medical journal, Science Translational Medicine.