Filling the Gaps

Christine Bowen
September 01, 2002
cells under microscope on top and dyed on bottom
Jennifer Jewell

Bone Cells (above) show the effects of breast cancer when tagged with fluorescent dyes. Comparing the numbers of breast cancer cells (green) and dead cells (red) could help determine why breast cancer spreads to bone.

Maria, 32, led a full life. Keeping up with her children was a challenge, but David and Christina were a constant source of energy as well.

Then the energy level changed: Maria was diagnosed with breast cancer and had to have a mastectomy. After surgery, she endured a year of chemotherapy. The thought of the disease recurring was frightening; both her grandmother and aunt had died from ovarian cancer. Her tumor had been found late, when there is an 85 percent chance that the cancer will invade other tissues. Seventy percent of these metastases occur in the bone and lungs. If her cancer moved to the bone, Maria's chance of dying from the disease would increase to 90 percent. She would be unaware of the deterioration of her bones until painful, fracture-inducing lesions already existed. Once cancer has moved to bone, it can not be surgically removed.

Andrea Mastro, a professor of microbiology and cell biology, and a team of students at Penn State are working to understand why breast cancer spreads to bone. The problem, Mastro says, hinges on osteoblasts, the cells responsible for building new bone. The lab has evidence that some osteoblasts undergo apoptosis, or "programmed cell death," when exposed to cancer cells.

"The surface molecules of bone cells and cancer cells have some of the same proteins," says Mastro. Because the cells share these proteins, the tumor cells may manipulate other cells into thinking they belong in the bone.

A protein called fas, found on osteoblasts, may be binding to a receptor called the fas-ligand on breast cancer cells, which signals for the normal cell to die. Mastro hopes to collaborate with drug companies on a treatment to stop the cells' deaths. "Right now drug companies target osteoclasts," cells that break down old bone, says Mastro. "The feeling is, If we can keep osteoclasts from destroying the bone, we can help cure the metastases. That isn't true. You don't know there is a metastasis until a hole already exists." With no bone-building cells left to refill the holes, a drug that targets osteoclasts alone will not be enough.

Lining the walls of Mastro's lab are thousands of beakers and test tubes stacked in old wooden shelves; microscopes, centrifuges, and folders rest on dingy black countertops. Two large refrigerators contain millions of antibody molecules, colored green and red; when magnified, the colors identify different types of molecules and proteins.

In the back of the lab, sitting with her hands beneath a large biohazard hood, undergraduate student Michelle Kinder investigates one of the biochemical pathways in cancer cells. As she explains, "The cancer cells may be secreting the protein wnt, which causes the osteoblasts to secrete the protein wisp. The wisp could then act to allow more rapid growth of the cancer cells, causing the pathway to continue." Healthy bone cells are thus tricked into helping the cancer grow.

Kinder has also been working with lab technician Jennifer Jewell counting apoptotic cells—those cells in the process of programmed cell death—with a computerized microscope. Counting these cells is important to prove that the cancer cells actually cause the osteoblasts to die.

Kristin Guttridge, who has worked in Mastro's lab for over two years, is looking at what causes apoptosis. Using an instrument called a flow cytometer, she compares the levels in the cell of the specific protein and receptor which aid in cell death. The flow cytometer uses lasers, optics, and electrons to measure cell properties. A test tube containing millions of cells is inserted into an opening in the machine, which "one by one sucks out the cells and detects fluorescence," says Guttridge. A fluorescent stain labels the protein fas and the receptor fas-ligand. The presence of the two together signals apoptosis.

Robyn Mercer, a graduate student, examines the maturation of cells. "I hypothesize that the presence of cancer is altering the ability of the osteoblasts to mature," she says. Her research will help to understand why osteoblasts, once in contact with cancer cells, no longer lay down bone to fill in the lesions caused by osteoclasts.

Will the team's research help Maria? Fortunately, Maria has beaten the disease. She defied the odds a second time when she gave birth to her third child, Peter, conceived a month after her last chemotherapy treatment. "I feel really good about myself," she writes. Her story, along with those of other cancer survivors, is featured in the book Show Me: A Photo Collection of Breast Cancer Survivors' Lumpectomies, Mastectomies, Breast Reconstructions and Thoughts on Body Image, published by the Women's Health Center of Penn State's Hershey Medical Center.

Kristin Guttridge and Michelle Kinder are members of WISER (Women in Science and Engineering Research) and the Schreyer Honors College and are working toward degrees in biochemistry and molecular biology in the Eberly College of Science. Robyn Mercer is a graduate student in the Eberly College of Science. Jennifer Jewell is a laboratory technician. Andrea M. Mastro, Ph.D., is professor of microbiology and cell biology in the Eberly College of Science, 431 S. Frear Lab, University Park, PA 16802; 814-863-0152; Mastro collaborates with Carol Gay, Ph.D., professor of cell biology and poultry science in the Eberly College Science, and Danny Welch, Ph.D., associate professor of pathology in the College of Medicine. The project is funded through a Life Science Consortium Biotechnology Innovations Grant. For more information on the book Show Me, see Writer Christine Bowen graduated in May 2002 with a B.A. in journalism.

Last Updated January 10, 2014