Why We Don’t Get Cancer All the Time

Why We Don’t Get Cancer All the Time

December 13, 2007

(PHILADELPHIA – December 14, 2007) – The seemingly inefficient way our bodies replace worn-out cells is a defense against cancer, according to a new study co-authored by scientists at The Wistar Institute.

Having a neighboring cell just split into two identical daughter cells would seem to be the simplest way to keep bodies from falling apart. However, that would be a recipe for the kind of genetic mutation that leads to uncontrollable cell proliferation – and cancer.

Instead, multicellular organisms use a seemingly inefficient process to replace lost cells. When replacement cells are needed, epithelial tissues such as those in the skin call upon stem cells, which differentiate, or grow into different types of cells. Some divide to make transient amplifying cells, or TACs – intermediate cells that in turn divide to produce skin cells. The new skin cells are evolutionary dead ends; they cannot reproduce.

Cells that self-renew, or make copies of themselves, instead of differentiating are more vulnerable to cancer, says Carlo C. Maley, an assistant professor in The Wistar Institute’s Molecular and Cellular Oncogenesis Program and senior author of the study. Maley and his colleagues published their paper, “Animal Cell Differentiation Patterns Suppress Somatic Evolution,” in the December 14 issue of PLoS Computational Biology. 

“Somatic evolution” refers to mutations that can occur in somatic cells over an organism’s lifetime. The process of cellular differentiation flushes these mutant cells from our bodies.

In their study, the researchers compared mutations in different modes of cellular reproduction. They found that if cells reproduce by simply making carbon-copies of themselves, their descendants are more likely to accumulate mutations. In contrast, if cellular reproduction was much more complicated, the cells’ descendants had fewer mutations.

Suppressing mutations that might fuel uncontrolled growth of cells would be particularly important for larger organisms that had long lives, the team wrote in their research report.

The earliest mutation in the cancer process often occurs in a gene that controls differentiation, Maley notes. It is unclear, however, which mutations are necessary to cause cancer in humans, and this study lays the foundation for investigating that question.

“It looks like it’s easier to prevent cancer than to cure it,” Maley says, “and we’d like to understand the earliest processes in carcinogenesis.”
Additional studies will further explore the cellular mutations that give rise to cancer and the dynamics of the interactions between stem cells and other cells.

John W. Pepper of the University of Arizona and the Santa Fe Institute is lead author on the study. Maley’s co-author at Wistar is Kathleen Sprouffske, who is also affiliated with the University of Pennsylvania.

The National Institutes of Health, the Pew Charitable Trust, the Commonwealth Universal Research Enhancement Program of the Pennsylvania Department of Health, and the Santa Fe Institute funded the research.

The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. Discoveries at Wistar led to the creation of the rubella vaccine that eradicated the disease in the United States, human rabies vaccines used worldwide, and a rotavirus vaccine approved in 2006. Today, Wistar is home to preeminent research programs studying skin cancer, lung cancer, and brain tumors. Wistar Institute Vaccine Center scientists are creating new vaccines against pandemic influenza, HIV, and other diseases threatening global health. The Institute works actively to transfer its inventions to the commercial sector to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today’s Discoveries – Tomorrow’s Cures. On the web at www.wistar.org.