NEW CANCER-FIGHTING DRUGS POSSIBLE THROUGH STUDIES AT ARGONNE
16 May 2005 - DOE/Argonne National Laboratory

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 angiogenesis.

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, Argonne biologist Diane Rodi explains. 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. Humans only grow capillaries when healing from an injury or during menstrual cycles," says Rodi. "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 disable tissue function.

"Tumors kill by invading the body's normal tissues and crowding them out, preventing them from doing their job," says Rodi. "A patient dies because those tissues cannot function properly."

Capillaries are formed by endothelial cells that form 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 new capillaries.

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 during the eight-hour capillary formation process.

The biologists identify the isolated RNA and, since RNA codes for proteins, determine what proteins the cells are making at each time interval.

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