In a breakthrough study appearing in the journal Nature Methods, researchers at Albert Einstein College of Medicine of Yeshiva University describe for the first time a method of viewing individual breast cancer cells for several days at a time. The study, by scientists in Einstein's Gruss Lipper Biophotonics Center, provides detail on how cancer cells invade surrounding tissue and reach blood vessels. These movements are the first steps of the potentially deadly stage of cancer known as metastasis.

Using intravital imaging, the researchers developed a "photoswitch" to mark cancer cells of their choosing within a tumor and observe how these tumor cells in mice move in their surrounding tissue. The technique allowed researchers to see individually labeled tumor cells move in real time and in living mice.

"One focus of our laboratories has been developing methods to see what cancer cells are doing when followed over time in the most realistic setting," said Jeffrey Segall, Ph.D., professor of anatomy and structural biology.

"Mapping the fate of tumor cells in different regions of a tumor was not possible before the development of the photoswitching technology," explained John Condeelis, Ph.D., co-chair and professor of anatomy and structural biology and co-director of the Gruss Lipper Biophotonics Center.

The new method involves the placement of a frame containing a small glass window onto the breast tumor of a mouse formed from cancerous cells that have a specific tag. Through the glass, individual breast tumor cells are targeted with a laser that 'marks' the cancer cells red. By viewing the cells through the window using a microscope, researchers can follow the cells as they spread. The mouse can move around and live normally with the glass plate and then be anesthetized briefly for observance under the microscope. The marked cancer cells are followed over a period of days until they lose their brightness.

Using this technique, investigators found that breast cancer cells closer to blood vessels were more aggressive and directed in their invasiveness than cancer cells farther from blood vessels. The cancer cells near blood vessels also appeared in the lung indicating that they are disseminated throughout the body.

This finding marks the first time a direct link was shown between the presence of blood vessels and the invasive ability of a cancer cell, which strengthens the growing theory that blood supply is crucial to effective metastasis. It also suggests that many cancer therapies currently in development, which are directed at cutting off blood supply to tumors, may be on the right track.

SOURCES:
Nature Methods, online edition, November 9, 2008
Albert Einstein College of Medicine of Yeshiva University (http://www.aecom.yu.edu)