Aging cells may promote tumors nearby

Growing old can rob a person of hair, strength, agility, clear vision, and mental sharpness. It also raises one’s chance of getting cancer. Cancer rates go up exponentially in the final decades of life.

“Age is the most important of all carcinogens,” notes Ronald A. DePinho of the Dana-Farber Cancer Institute in Boston.

Offering a link between aging and cancer, a research team has found that cells in a nondividing state called senescence can stimulate cancer-prone cells to grow into tumors. The finding is unexpected because scientists suspect that senescence evolved as a mechanism to prevent cancer in the early years of long-lived animals.

Decades ago, investigators noted the tendency of aging human cells in laboratory dishes to eventually stop dividing and alter their shape and genetic activity. This led researchers to suggest that a buildup of these senescent cells in the body contributes to age-related deterioration. They also proposed that senescence helps check uncontrolled division, the hallmark of cancer, among these cells (SN: 1/3/98, p. 7).

While senescent cells themselves may not grow into tumors, their altered function may promote cancer in neighboring cells that have accumulated mutations with age, scientists now report.

Good early in life and bad later, senescence is a “double-edged sword,” concludes Judith Campisi of Lawrence Berkeley (Calif.) National Laboratory. She and her colleagues report their findings in the Oct. 9 Proceedings of the National Academy of Sciences.

Breast, prostate, and the other cancers that most increase in frequency with age grow from cells that line ducts, glands, and surfaces of organs. Providing a base for these epithelial cells is the stroma, a tissue that includes cells called fibroblasts. The interactions between epithelial and stromal cells are central to the process by which an epithelial cell with cancer-predisposing mutations develops into a full-fledged tumor, Campisi and her colleagues now contend.

This “symbiotic relationship” is the “next great frontier in cancer research,” says DePinho. The microenvironment around a cancer-prone, or precancerous, cell can either promote or suppress its growth into a tumor, adds Campisi.

In 1997, Campisi proposed that senescent cells play a role in age-related cancers. Now, she and her colleagues show that senescent human fibroblasts stimulate proliferation of precancerous and malignant human cells, both in lab dishes and in mice. Simultaneous injections of senescent cells and mutated human epithelial cells produced many more tumors in mice than injections of the epithelial cells alone did.

When the researchers injected mice with a mix of senescent cells and aggressive human breast cancer cells, the breast cells formed tumors even more quickly than the cancer cells did on their own.

The senescent fibroblasts stimulated the growth only of cells with pre-existing mutations that predisposed them to cancer. “Senescent cells have no effect on normal cells in regard to cancer growth,” says Campisi.

Molecules secreted by the senescent cells play a large role in stimulating tumor growth, the investigators conclude from test-tube experiments in which the fibroblasts were kept from direct contact with the epithelial cells. Therapies that selectively kill senescent cells or turn off their secretions may help prevent some age-related cancers, suggests Campisi.

While calling the new study important, DePinho cautions that senescence isn’t the only connection between aging and cancer. He points to other age-related factors, such as declining immune function and dwindling telomeres, the protective tips of chromosomes that shrink with every cell division.

“It is likely that multiple mechanisms contribute to the increase of cancer with age,” says DePinho.