June 23, 2014 | Researchers from University of Arkansas for Medical Sciences (UAMS) and Albert Einstein College of Medicine in New York have developed a new technological approach for tracking individual circulating tumor cells (CTCs) in the bloodstream, helping researchers identify the pathways of single cancer cells inside the body and possibly leading to the development of new ways to prevent the spread of cancer.

“The approach may give oncologists a method to track individual CTCs and distinguish the behavior of metastatically aggressive CTCs from other ones. We hope, this knowledge will lead to development new therapeutic approaches to target only dangerous CTCs, and, eventually, to intervene and stop cancer more effectively,” said Ekaterina Galanzha, M.D., Ph.D., and an associate research professor in the UAMS College of Medicine’s Department of Otolaryngology, Head and Neck Surgery.

The findings of Galanzha as a leader of this research were recently published in Chemistry & Biology, a prestigious scientific journal. UAMS team includes also Vladimir  Zharov, Ph.D., D.Sc., senior scientist in the UAMS Winthrop P. Rockefeller Cancer Research Institute, and Dmitry Nedosekin, Ph.D., UAMS College of Medicine research associate in the UA.

Up to 90 percent of all cancer deaths are caused by metastases (spread of cancer) produced by CTCs. Fortunately, only less than 0.01 percent of CTCs are able to form metastases. Therefore, there is a crucial need to detect these metastatically aggressive CTCs. The significant progress has been made in molecular characterization of CTCs while the behavior patterns of aggressive CTCs remains almost unclear.

The new approach so-called in vivo photoswitchable flow cytometry uses photoswitchable fluorescent proteins that can change their color in response to light and that can be genetically incorporated into cancer cells. To label (change color) individual CTCs, very thin laser beam with a diameter comparable to the diameter of one cell was focused into a small blood vessel. This schematic allows labelling the controlled number of cells, even one CTC because only one CTC passes laser beam at a moment of time. To extend the capability of photoswitchable flow cytometry, researchers integrated three thin parallel laser beams operated at different wavelengths. Thus, CTCs are counted before labeling with the first laser beam, then some of these can be labeled with the second laser beam, and labeling efficacy is estimated with the third laser beam. Furthermore, this technical platform tracks labeled CTCs over a period of time. The obtained information from each cell is collected, detected and reproduced on a computer monitor as real-time signal traces, allowing the investigators to count and track individual CTCs in the bloodstream.

“This technology allows for the labeling of just one circulating pathological cell among billions of other normal blood cells by the ultrafast changing color of photosensitive proteins inside the cell in response to laser light,” Galanzha said.

Researchers were able to monitor the real-time dynamics of CTCs released from a primary tumor, and then image the various final destinations of individual CTCs. They observed how these cells circulate and colonize healthy tissue or the site of the primary tumor (self-seeding phenomenon). Researchers also demonstrated the images of cancer cells that colonize tissue but did not grow (so-called dormant cells). For the first time, they visualized that CTCs are able to enter existing metastases (reseeding phenomenon). The significance of this phenomenon for metastasis progression will be explored in the upcoming experiments.

The approach also might prove useful for other areas of medicine — for example, tracking bacteria during infectious sepsis or immune-related cells during the development of autoimmune diseases.