In a study published in the December issue of Cancer Cell, the team showed that stem and progenitor cells are susceptible to a specific error during cell division that can result in severe 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 explain how a cancer stem cell acquires additional 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 nature of cancer stem cells could result in new therapies that specifically target those cells, which are thought to be the driving force of tumor progression.
The process of cell division is closely monitored by the cell, because a mistake can result in a cancer-causing chromosome abnormalities. Typically during cell division, cells monitor quality control with a series of checkpoints. One such checkpoint confirms that the cell's chromosomes have been disentangled before they are to be pulled apart in mitosis, to ensure that the chromosomes will be separated appropriately.
The Columbia researchers found, however, that stem and progenitor cells are deficient in this checkpoint and will divide even if the chromosomes are entangled. All three cell types tested by the researchers - mouse embryonic stem cells, mouse neural progenitor cells, and human bone marrow progenitor cells - attempted cell division with entangled chromosomes. The researchers think 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," said Dr. Best
Contact: Craig LeMoult
Columbia University Medical Center