It has been known for many decades that normal tissue stem cells produce daughter cells with differing potentials for self-renewal and specialization through a process called asymmetric cell division. An immortal DNA strand hypothesis states that stem cells asymmetrically divide their DNA strands during cell division as a means to prevent DNA replication errors. While some evidence for the immortal DNA strand hypothesis exists in normal stem cells, the theory has never been proven and has never before been tested in cancer cells.
To investigate the immortal strand hypothesis in human lung cancer cells, NCI scientists performed a series of experiments termed ‘pulse-chase’ procedures. They found that a small population of laboratory lung cancer cells as well as cells in lung tumor samples asymmetrically divided their DNA strands. They also found that the frequency of asymmetric division could be modulated by changes in the cell’s microenvironment, suggesting the process may be regulated by neighboring cells as well as by other factors. The scientists then discovered that asymmetric division of DNA correlates with the lung cancer stem cell marker, CD133. The characterization of asymmetric cell division and its modulation in lung cancer cells provides insights into tumor initiation, self-renewal, and growth, as well as strategies to develop novel targets for treatment. Future work will aim to link this division to the cancer stem cell hypothesis.