Possible Tumor Growth Mechanism Found

In a study published in the December 2005 issue of the journal Cancer Cell, a group of researchers from Columbia University Medical Center (CUMC, New York, NY, USA) reported that stem and progenitor cells are vulnerable to a certain error during cell division that can result in serious chromosomal defects. This susceptibility may explain how a tumor-initiating cell, also known as a cancer stem cell, arises from a normal cell. It may also clarify how a cancer stem cell acquires further mutations that increase tumor malignancy.

According to Timothy Bestor, Ph.D., and Marc Damelin, Ph.D., of Columbia University College of Physicians and Surgeons, understanding the character of cancer stem cells could result in new therapies that specifically target those cells, which are believed to be the underlying cause of tumor progression.

The process of cell division is closely tracked by the cell, because an error can result in cancer-causing chromosome abnormalities. Normally, during cell division, cells monitor quality control with a series of safeguards. One such safeguard confirms that the cell's chromosomes have been unscrambled before they are to be pulled apart in mitosis, to ensure that the chromosomes will be separated appropriately.

The researchers discovered, however, that stem and progenitor cells are deficient in this safeguard and will divide even if the chromosomes are entangled. All three cell types evaluated by the researchers--mouse embryonic stem cells, mouse neural progenitor cells, and human bone marrow progenitor cells--attempted cell division with entangled chromosomes. The investigators believe it likely that cancer stem cells, which closely resemble normal stem cells, have the same deficiency.

"The failure to untangle before dividing undoubtedly will lead to chromosomal defects,” stated Dr. Bestor, professor of genetics and development at Columbia and the study's chief investigator. "Surviving cells may end up with too many chromosomes, they may lose chromosomes, or some chromosomes may get rearranged.” These same kinds of chromosomal defects are the hallmark of cancer cells, and there are chromosomal defects in all types of cancer.

"We may have found how a stem cell without any pre-existing mutation can become a cancer stem cell,” noted Dr. Damelin, a CUMC postdoctoral fellow of the Damon Runyon Cancer Research Foundation and the lead author on the study.

The study also demonstrates the potential problems involved with stem cell therapies. In the lab, stem cells are stimulated to divide many times more than they typically would divide in an organism. The more stem cells divide, the more apt they are to acquire abnormal chromosome characteristics. However, the investigators reported that additional studies will be needed to understand and address these risks.






Related Links:
Columbia University Medical Center