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Colleen Kuemmel, a scientific assistant in the Biosciences Division, makes adjustments to a light microscope to get a clearer view of endothelial cells four hours after adding growth factors. The microscope is attached to a digital camera. Biologists take snapshots every half-hour to monitor capillary growth in their petri dishes. |
Proteins discovered that could cut tumor growth |
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Proteins that could lead to drugs that stop tumor growth and cancer have been identified by Argonne biologists studying capillary formation, or angiogenesis. Argonne researchers are the first to study the earliest steps in capillary formation in tumors. They identified 280 proteins that endothelial cells—cells that form blood vessels—secrete in large quantities during capillary growth. Because proteins are responsible for cellular structure and communication, biologists want to learn which ones to block to develop a treatment that arrests tumor growth by halting capillary formation. While anti-angiogenic drugs have shown promise in laboratory studies, they have not fared well in clinical trials. That is because they have targeted only individual molecular pathways, explained Diane Rodi, a biologist in the Biosciences Division. Researchers expect their in-depth angiogenesis work to find more effective treatments. Current cancer therapies attack fast-dividing cells, such as hair follicles and the cells that line the gastrointestinal tract, causing side effects of nausea and hair loss. “There is not a lot of capillary growth in normal adults,” said Rodi. “Humans only grow capillaries when healing from an injury or during menstrual cycles. So if we can come up with a cocktail of drugs to knock out all capillary formation in the body, it might be a method of treating cancer patients that does not make them sick.” Capillaries are a tumor’s lifeline, delivering oxygen to and removing waste from it. Tumors use capillaries to metastasize, or spread to other body tissues. When malignant tumors move to other body tissues, they crowd healthy cells and prevent them from functioning properly, making cancer fatal. Capillaries are formed by endothelial cells that create little hollow tubes. When a tumor lacks oxygen, it sends protein signals toward existing capillaries. Endothelial cells break off, releasing enzymes that chew through body tissue toward the tumor to make a new capillary. Argonne’s Angiogenesis Group mimics natural capillary formation. Endothelial cells that have been isolated from human tissue and mixed with growth factors are placed in a protein gel. The gel acts like body tissue and causes the cells to release enzymes. Using a light microscope attached to a digital camera, the group takes snapshots of the cells and isolates their ribonucleic acid (RNA) during the eight-hour capillary formation process. The biologists identify the isolated RNA that codes for proteins to determine what proteins the cells produce at each time interval. Also see: http://www.anl.gov/OPA/logos21-2/capillaries01.htm. For more information, please contact Evelyn Brown. Next: Scientific
disciplines blur as researchers work |