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Pitt Scientists Study How Cancer Cells Get Out Of Control

Date:
January 19, 2005
Source:
University Of Pittsburgh Medical Center
Summary:
Researchers at the University of Pittsburgh have identified how a single aberrant cell can duplicate to form cancerous tumors, suggesting a specific protein mechanism as a target for the treatment of cancer, they report in a paper titled "Spindle Multipolarity Is Prevented by Centrosomal Clustering," published in the Jan. 7 issue of Science.

PITTSBURGH, Jan. 6 -- Researchers at the University of Pittsburgh have identified how a single aberrant cell can duplicate to form cancerous tumors, suggesting a specific protein mechanism as a target for the treatment of cancer, they report in a paper titled "Spindle Multipolarity Is Prevented by Centrosomal Clustering," published in the Jan. 7 issue of Science.

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The team, led by William S. Saunders, associate professor of biological sciences in Pitt's School of Arts and Sciences, found that overexpression of a single protein can cause changes in a cell associated with the formation of tumors.

"Virtually all cancer cells acquire the ability to change their genomic structure," said Saunders. "Researchers in the field are looking for single events that can cause multiple mutational changes to the genome, and this research is an example of that."

Before a normal cell divides, its chromosomes are duplicated and then pulled apart by a structure called a spindle, so that the two daughter cells each will have the same number of chromosomes.

At the end of a normal spindle is the spindle pole, also called the centrosome, which pulls the chromosomes outward. Cancer cells often have extra centrosomes. When a cell has more than two centrosomes, sometimes--but not always--the spindles will have more than one pole and cell division won't work correctly, leading to the swapping of genetic material, uncontrolled cell division, and the formation of tumors.

Why this doesn't always happen when there are too many centrosomes was the focus of the Pitt researchers' investigation. They found that as long as the extra centrosomes "cluster" together, the spindles will form normally, with two ends, and the cells will divide normally. "No one else appreciated that that was required, or what the mechanism was that separated them," said Saunders.

But when the extra centrosomes don't cluster together, the spindles don't form normally, and cell division can become unstable, reported Nicholas J. Quintyne, a postdoctoral fellow working with Saunders and first author of the paper.

Investigating the mechanism by which this occurs, the researchers found that in cultured oral cancer cells a protein called dynein is missing from the spindle, and the centrosomes no longer cluster together.

Furthermore, the researchers discovered that in some types of tumors, dynein is inhibited by the overexpression of another protein called NuMA. Excess NuMA seems to prevent dynein from binding to the spindle. When they reduced the level of NuMA in cultured cancer cells, the dynein returned to the spindles, and the spindles were no longer multipolar.

"This finding suggests that a possible treatment for some types of cancer could be a drug that inhibits NuMA," noted coauthor Susanne M. Gollin, professor of human genetics in Pitt's Graduate School of Public Health and coinvestigator at the Oral Cancer Center of Discovery at the University of Pittsburgh Cancer Institute.

In the future, the researchers plan to look at other proteins that bind to NuMA and how these proteins interact in the process.

###

The research was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health and by the American Cancer Society.


Story Source:

The above story is based on materials provided by University Of Pittsburgh Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Pittsburgh Medical Center. "Pitt Scientists Study How Cancer Cells Get Out Of Control." ScienceDaily. ScienceDaily, 19 January 2005. <www.sciencedaily.com/releases/2005/01/050110123008.htm>.
University Of Pittsburgh Medical Center. (2005, January 19). Pitt Scientists Study How Cancer Cells Get Out Of Control. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2005/01/050110123008.htm
University Of Pittsburgh Medical Center. "Pitt Scientists Study How Cancer Cells Get Out Of Control." ScienceDaily. www.sciencedaily.com/releases/2005/01/050110123008.htm (accessed November 28, 2014).

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