Most common lung cancers may begin in newly discovered cells

ctions might be a stem cell niche.

Bender Kim and her co-authors first isolated the stem cells, which they named bronchioalveolar stem cells (BASCs), from the earliest stage of the mouse tumors. Then, she purified them from the lungs of healthy mice. On the surface of BASCs, Bender Kim found another protein marker that is also present on the surface of better-studied hematopoietic stem cells. She made certain that BASCs were not stem cells of the blood or blood vessels.

The BASCs passed the rigorous tests for stem cells. In response to two types of lung damage that killed the more specialized cells, BASCs proliferated and appeared to give rise to the Clara or alveolar cells lining the airways. In tissue cultures of normal mouse cells, only the BASCs could grow more of themselves or differentiate into Clara or alveolar cells. In tissue cultures of the mutant mouse lung cells, the activated oncogene only triggered growth of the BASCs, not of the more specialized alveolar cells.

"The stem cells may retain mutations from the same damage that kills the more specialized cells," Bender Kim speculates. "If the DNA is not repaired properly, and if the mutation happens to affect a tumor suppressor gene or oncogene, it could start the process of forming a tumor. There are certainly suggestions that various tumors might arise in locations where there has been a previous injury."

The researchers acknowledge that the ultimate stem cell test remains. "One thing we have not done is taken BASCs and put them back into the mouse and show in vivo that they perform as stem cells," Bender Kim said. "We don't have an assay for that yet."

With hematopoietic stem cells, for example, scientists can inject the stem cells into the bone marrow of an irradiated mouse and replace the entire blood system, the basis of bone marrow transplantation. Solid tissue is trickier. Bender Kim and her colleagues do not yet know the optimal microenvironment for stem

Contact: Jim Keeley
Howard Hughes Medical Institute

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