Prospective identification of tumorigenic breast cancer cells

M Al-Hajj, MS Wicha… - Proceedings of the …, 2003 - National Acad Sciences
M Al-Hajj, MS Wicha, A Benito-Hernandez, SJ Morrison, MF Clarke
Proceedings of the National Academy of Sciences, 2003National Acad Sciences
Breast cancer is the most common malignancy in United States women, accounting for>
40,000 deaths each year. These breast tumors are comprised of phenotypically diverse
populations of breast cancer cells. Using a model in which human breast cancer cells were
grown in immunocompromised mice, we found that only a minority of breast cancer cells had
the ability to form new tumors. We were able to distinguish the tumorigenic (tumor initiating)
from the nontumorigenic cancer cells based on cell surface marker expression. We …
Breast cancer is the most common malignancy in United States women, accounting for >40,000 deaths each year. These breast tumors are comprised of phenotypically diverse populations of breast cancer cells. Using a model in which human breast cancer cells were grown in immunocompromised mice, we found that only a minority of breast cancer cells had the ability to form new tumors. We were able to distinguish the tumorigenic (tumor initiating) from the nontumorigenic cancer cells based on cell surface marker expression. We prospectively identified and isolated the tumorigenic cells as CD44+CD24−/lowLineage in eight of nine patients. As few as 100 cells with this phenotype were able to form tumors in mice, whereas tens of thousands of cells with alternate phenotypes failed to form tumors. The tumorigenic subpopulation could be serially passaged: each time cells within this population generated new tumors containing additional CD44+CD24−/lowLineage tumorigenic cells as well as the phenotypically diverse mixed populations of nontumorigenic cells present in the initial tumor. The ability to prospectively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival. Furthermore, because these cells drive tumor development, strategies designed to target this population may lead to more effective therapies.
National Acad Sciences