Technology Transfer

Space Bioreactor Helps Understand Breast Cancer

A SPECIAL INCUBATOR DESIGNED TO GROW tissue samples in space is being applied on Earth to help understand how breast cancer works and how it might be controlled. Ground-based scientists are using NASA Bioreactors to culture breast cells and learn what controls the growth of both healthy and malignant breast tissues. Their findings could affect health care for women not only on Earth, but also on missions to Mars.

"We know that many things—radiation, certain chemicals, genetic makeup—can contribute to the cause of breast cancer," said Dr. Robert Richmond, director of the recently created Radiation and Cell Biology Laboratory at NASA's Marshall Space Flight Center in Huntsville, Alabama. Richmond is also a research associate professor of medicine at the Dartmouth Medical School in Hanover, New Hampshire.

"We are culturing noncancerous mammary cells, hoping to learn what guides their growth and how we might use that knowledge to thwart malignancies before they are created," Richmond added. "The type of mammary cells we are growing comes from an individual susceptible to breast cancer, and that susceptibility is likely driven by damage caused by ionizing radiation. Space exploration will involve slightly increased exposures of crew members to radiation, so what we learn from these cells could help justify methods of female crew selection, and help manage breast cancer in the national population at the same time."

Cancer research is typically a collaborative and interdisciplinary effort. Richmond was connected with a breast cancer-susceptible donor of the mammary tissue now used in his laboratory by Dr. Mike Swift of the Medical College of New York, Hawthorne. Drs. Olive Pettengill (Pathology Department of the Dartmouth Medical School) and Martha Stampfer (Lawrence Berkeley National Laboratory) helped him select cells from this cancer-susceptible breast tissue. Within NASA, Richmond also interacts with Dr. Jeanne Becker, an associate professor at the University of South Florida College of Medicine in Tampa, and with investigators in the Biotechnology Cell Science Program at NASA's Johnson Space Center in Houston, home of the NASA Bioreactor.

For many people, culturing cells means placing some small number into nutrient media in a dish or a tube and letting them grow, resulting in pancake shapes that offer limited insight. Without a proper three-dimensional assembly, epithelial cells (the basic cells that differentiate tissue into specific organ functions) lack the proper clues for growing into the variety of cells that make up breast tissue.

Cells self-associate in the body, meaning that replication involves associating with the proper connections in the surrounding environment (the body) for proper growth clues to naturally form. However, gravity's effects limit studying cell growth outside the body because, in an Earth gravity environment, the cells do not easily self-associate to grow naturally. A culture environment must closely, if not exactly, simulate tissue assembly in the body to enable the cells with the proper growth clues.

To solve the problem, in the 1980s, NASA developed the Bioreactor, a clear, can-like rotating vessel with a membrane for gas exchange that allows nutrients in and carbon dioxide and wastes out. As the Bioreactor turns, the cells continually fall through the medium yet never hit bottom, thus promoting the self-association of a proper growth environment. The cells then form clusters and grow and differentiate as they would in the body.

Therefore, Richmond and Becker are using NASA Bioreactors to fool mammary cells into thinking they are in a normal environment and thus culture them into larger assemblies whose natural growth can be studied. At Marshall Space Flight Center, Richmond has established a research program using a unique collection of healthy breast cells that contain a significant genetic weakness toward developing cancer. Becker, in collaboration with co-workers at Johnson Space Center, has grown primary breast cancer cells (obtained directly from different surgical specimens) into masses that resemble the original tumor. She hopes to further our understanding of the factors important in the growth and spread of tumors.

"We have grown noncancerous human breast cells in the NASA Bioreactor," Richmond said. "Our observations suggest there is much to learn, and value to be gained, from the study of their tissue-equivalent growth."

The culturing of primary breast cancer cells for long periods is rarely achieved in standard tissue culture dishes. With tumor cells from 27 different breast cancer patients, Becker could get only five specimens to grow enough to fill the dish. None of the five could then be expanded further when passed to new dishes. In contrast, however, tumor samples from another five breast cancer patients grew successfully for long periods of time as three-dimensional co-cultures in the NASA Bioreactor.

These primary breast tumor cell constructs were grown successfully for up to three months, and the cancerous fraction increased. These constructs grew up to three millimeters in diameter, at which point they were removed for analysis and thus prevented from additional growth. Eventually, in this Earth condition, the Bioreactor cell clusters become too large to fall slowly, and research has to be continued in the true weightlessness of space.

The information relating to the patient-derived breast cancer constructs grown in the Bioreactor by Becker and co-workers at Johnson Space Center suggests that this model simulates events that occur as breast tumors progress within the body. This line of research therefore offers potential for increasing knowledge on the basic biology of human breast cancer. For more immediate application, this research also provides, for the first time, an opportunity to test breast cancer therapies on a patient's cancer cells in culture before extending that therapy to the patient him- or herself.

With the healthy cells, Richmond is developing a normal breast tissue-equivalent model, a scientific description of how healthy breast tissue grows. A routine capability to model patient-specific breast cancer then could allow for testing and developing realistic therapies. For example, hormonal therapy is an important treatment option for approximately a third of previously untreated breast cancer patients. It is well known that breast tissue responds to estrogens. However, normal human mammary epithelial cells in a standard two-dimensional culture dish do not demonstrate any estrogenic response.

Richmond plans experiments that will determine whether three-dimensional constructs of normal breast tissue in the Bioreactor will respond to estrogen. If so, then Bioreactors could be used to tailor hormonal therapies that more closely match what will stop the growth of cancer cells, with minimal side effects for the patient.

To begin this research, Richmond established a cell repository from noncancerous breast tissue donated by a young woman carrying a single defective ATM gene. The debilitating syndrome ataxia-telangiectasia (A-T) results when both of the two ATM genes normally present in the body's cells become defective. These A-T individuals have about a 100-fold increased risk of all cancers plus other serious problems. Women carrying only one defective ATM gene are clinically normal, but have about a five-fold increased risk, or susceptibility, to breast cancer.

To reduce her breast cancer risk to near zero, the donor elected to have a double mastectomy. Her breast tissues now reside in a cell bank as perfectly matched cell types, preserved in liquid nitrogen, which will allow experimental results of today to be compared with experimental results obtained for many years to come.

In the Bioreactor, these cells will grow in normal fashion because they are normal except for the single defective ATM gene. Once the normal tissue-equivalent model is defined, then these same cells can be manipulated to mimic the stages of breast cancer formation, and the model-related differences can be evaluated. A normal tissue-equivalent model would thus hopefully promote the understanding of the creation of breast cancer and, eventually, allow for the development of therapies tailored to the individual patient.

For more information, contact Dr. Robert Richmond at Marshall Space Flight Center.
Call: 256/544-3418, E-mail: Robert.Richmond@msfc.nasa.gov
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Dr. Robert Richmond extracts breast cell tissue from one of two liquid nitrogen dewars. (Photo by Dennis Olive, NASA/Marshall Space Flight Center)

One of several Bioreactors used by Dr. Richmond in his research. (Photo by Dennis Olive, NASA/Marshall Space Flight Center)

A cross section of a construct, grown from surgical specimens of breast cancer and stained for microscopic examination, reveals areas of tumor cells dispersed throughout the nonepithelial cell background. The arrow denotes the foci of breast cancer cells. (Photo by Dr. Jeanne Becker, University of South Florida)