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Cellular senescence a double-edged sword
Date:12/3/2008

sion run amok. Nature has evolved two ways of shutting down cell-division and reining in uncontrolled growth: apoptosis, or cell suicide, and senescence, in which cells remain metabolically active but are no longer capable of dividing. Apoptosis as a tumor suppressor has been well characterized through in vivo studies, but the details of cellular senescence have not been so clearly defined. It was not until some 40 years after the process was first reported in cultures that an in vivo assay developed by Campisi and an earlier team of collaborators confirmed that it even occurs in living organisms.

Following her assay work, Campisi, a leading authority on cell senescence and the effects of aging, embarked upon studies in mice that led her to propose three years ago that with age an organism acquires enough senescent cells to create conditions in cells and tissue that are conducive to transforming benign lesions into malignant tumors. This hypothesis helped explain why tumor incidence increases exponentially with age.

"The evidence is increasing that genetic mutations alone are insufficient for cancer development," Campisi said when she first announced this hypothesis. "Rather, malignant tumors also require a permissive tissue environment in which to develop and progress."

In this latest research, she and her co-authors modified commercial antibody arrays to substantially improve their range and sensitivity, then measured the proteins secreted by senescent cells in culture, as well as from tissue samples that were collected from prostate cancer patients both before and after completing a DNA-damaging form of chemotherapy.

"We found that different types of cells from different tissue all secrete a remarkably similar set of proteins when they senesce in response to DNA-damaging radiation or chemotherapy," Campisi said.

She and her co-authors branded this set of proteins as a senescence-associated secretory phenotype, or
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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Cellular senescence a double-edged sword
Cellular senescence a double-edged sword
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