Dr. Christine Jurasinski
LabLearner Staff Scientist

What do you get when you combine a microscope, lasers, a mouse and some fluorescently labeled molecules? Well, if you are Erik Sahai and colleagues, you get the opportunity to discover why some cancer cells spread and why some do not.

In October 2009, Sahai published results that showed that a special protein called Transforming Growth Factor Beta (TGF β) acted as a signal for single breast cancer cells to leave a tumor and move through the blood to other areas of the body. What is even more fascinating is that he and his colleagues were able to visualize and capture the moving single breast cancer cells on video while these cells were still inside a living, breathing mouse!

So how was this research performed and how does it relate to what LabLearner students are currently studying? For LabLearner students, Sahai’s research combines concepts of microscopy, light, optics, proteins, cells and cancer that students investigate in the Microscopic Explorations, Light and Optics, Light, Genes and Proteins, and Cell Cycle and Cancer CELLs.

Although the Microscopic Explorations CELL is not the first time LabLearner students work with the compound microscope, it is the first time they use it to investigate animal, plant and bacterial cells. In this CELL students explore how changes in resolution and field of view can provide different types of information about cells and the structures within CELLs. Understanding these concepts provides the groundwork for the principles of microscopy and a framework for thinking about how microscopy can be used to study various cellular and microscopic questions. In the case of this latest research, students may be surprised to find that microscopy can be performed on living tissues and animals. However, when discussed, student should be able to understand the terms resolution and field of view and to appreciate some of the differences between their compound microscope and the confocal microscope used in this research.

For 4th and 6th grade students who perform the Light and Optics and Light CELLs, this latest discovery illustrates how knowledge of the electromagnetic spectrum and the wavelength of light can be applied in the forms of lasers and in the field of microscopy.

For 7th grade students, Sahai’s research provides an example of how concepts they learned from the Genes and Proteins and Cell Cycle and Cancer CELLs are not separate, but rather merge as scientists approach “real-life” problems. From these two CELLs, students should understand that cells proceed through a programmed sequences of events called the cell cycle that result in DNA synthesis and cell division. During the cell cycle, proteins are produced from a series of processes involving DNA and RNA. Changes in genes and proteins can result in changes in how the cell cycle is regulated, and some changes in cell cycle regulation can result in cancer and in the metastasis of cancer cells.

This newest research illustrates only one of the signals that scientists think causes cancer cells to metastasize. To answer the question of why some cancer cells leave a tumor and others do not, Sahai and his colleagues attached a fluorescent molecule to a protein located within breast cancer cells in mice. The protein would “glow” blue when it was activated. This protein was special in that another protein called TFG β could only activate it or turn it on. As a result, if TGF β turned on the protein, it glowed blue. Sahai then used a technique called multiphoton confocal microscopy to visualize the breast cancer cells within the mice. Multiphoton confocal microscopy is unique in that it is a non-invasive way to look at cells within a specimen, culture of living cells, living tissue or living organism. It involves using a laser to excite the fluorescent molecules in a sample. The laser sends a certain wavelength of light through the specimen. When the light hits the fluorescent molecule, another wavelength or “color” of light is given off. In this case, the color blue. A scanner at another part of the microscope detects the blue light and records its presence. All of this happens over a very small space of the sample. As the laser moves through the sample, any fluorescent light is recorded. Computers then build a digital, three-dimensional image of the fluorescent area of the sample.

For this study, mice that had fluorescently labeled proteins in their cells were given anesthesia and placed under the objective of the confocal microscope. The laser was then able to non-invasively scan or “section” the area of the breast cancer tumor as well as other areas of the body. Using this technique, Sahai and his colleagues were able to show that single cells that broke off of the tumor “glowed blue.” That is, they received a signal from the protein TFG β. Sahai was able to follow these cells as they traveled through the blood to other areas of the body including the lungs. In addition, the researchers found that while the genes activated by TFG β were turned on, the breast cancer cells could move but could NOT attach to other organs. Only when the genes activated by TFG β were turned off (the cells no longer glowed blue) could the cancer cells attach to other organs. In other words, TFG β acted as a switch for the activity of the single cancer cells. When genes were turned on by TGF β, the cancer cells could metastasize (move), but they could not attach to an organ or further divide. Only when the signal from TGF β was no longer present could the cancer cells attach to an organ and begin dividing and creating another tumor.

In contrast, Sahai found that cancer cells that broke off in clumps from the tumor were NOT activated by TFG β. That is they did not glow blue. Because these cells broke off in clumps, they could not cross the lymphatic barrier from the tissue into the blood and stayed within the breast tissue. That is they were unable to metastasize to other areas of the body.

These finding represent a significant leap in understanding how metastases occur and which cells present the most danger for the spread of cancer.

As for LabLearner students, Sahai’s research illustrates exactly what the power of combining concepts can do. His research takes us one step closer to understanding the spread of cancer and to potential new therapies that can be used to stop and treat the disease.