Faustian Bargain: Cellular senescence at first prevents, later promotes, cancer

Abstract

What seems like a good idea can sometimes backfire later. A mechanism that foils cancer in young animals might induce it in older ones, according to a new study. Most mammalian cells, whether in animals or culture dishes, don't divide forever; instead, they eventually undergo cellular senescence, which permanently arrests cell division (see "More Than a Sum of Our Cells" ). In animals, that process might prevent cells with DNA damage or shortened telomeres from growing into tumors (see "Dangerous Liaisons" ). Senescent cells, however, remain in the body--dormant but perhaps not benign. To investigate how senescent cells affect the tissue in which they reside, Krtolica and colleagues grew cultures that contained either presenescent or senescent fibroblasts--cells that compose connective tissue--and then layered test cultures of various epithelial cell types on top of the fibroblasts. The researchers measured proliferation of the epithelial cells by tagging their DNA with fluorescent labels. Senescent, but not presenescent, fibroblasts provoked duplication of cell lines that had previously acquired mutations known to predispose them to cancer, the team found. Neither senescent nor presenescent fibroblasts promoted the growth of normal human epithelial cells. Cell-to-cell contact isn't required for the stimulation: Material secreted by senescent cells induced precancerous cells to grow approximately three times faster than did material secreted by presenescent cells. Senescent cells also appear to promote tumor growth in vivo: Tumors were more prevalent and grew larger in mice injected with precancerous epithelial cells and senescent fibroblasts than in those injected with precancerous cells and presenescent fibroblasts. Senescent cells apparently create a rich environment for tumor growth. This phenomenon, combined with the increased incidence of cancer-causing mutations as time passes, could partially explain the exponential increase in cancer rates as we age. Identifying exactly how senescent cells create fertile ground for cancer might well shed light on how a good deal in youth turns sour with age. --R. John Davenport; suggested by Nick Bishop A. Krtolica, S. Parrinello, S. Lockett, P.-Y. Desprez, J. Campisi, Senescent fibroblasts promote epithelial cell growth and tumorigenesis: A link between cancer and aging. Proc. Natl. Acad. Sci. U.S.A. 98 , 12072-12077 (2001). [Abstract] [Full Text]