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Most common lung cancers may begin in newly discovered cells

and stem cells can give rise to different types of cells."

The researchers do not know if the stem cells play a role in more established tumors, but other scientists have found evidence that some human cancers contain a small but virulent group of cells known as "cancer stem cells" that regenerate the tumor, a capacity that most cells in a tumor lack.

"They may be the cells that we have to eliminate in cancer in order to obtain durable cures for the disease," said Jacks. "Along the way, we need to know how these cancer stem cells become different from normal stem cells."

Bender Kim started with a mouse model of non-small cell adenocarcinoma recently developed by another postdoc and graduate student in Jacks's lab to study the progression of lung cancer and the effects of conventional and experimental therapies.

The mouse carries a silent genetic mutation of an oncogene known as K-ras, which is found in about one-third of all tested non-small cell lung cancers in people. A specially designed virus can activate the mutation in only a few cells. The mouse is known as a conditional mutant strain. In this case, the mouse inhales a small amount of virus that activates the K-ras oncogene in some of the lung cells.

Four years ago, Jacks's lab reported that some of the resulting cancer cells carry the molecular markers of both of the two kinds of cells found in non-small lung cell cancers. In mice, the tumors start deep in the lung, past the trachea and the branches to the lobes. Ciliated cells that catch debris give way to the bronchiolar cells called Clara cells. The airways end with the alveolar cells, which are the grape-cluster-like sacks lined with microscopic vessels, where oxygen and carbon dioxide are exchanged.

At the junction of the bronchioles and alveoli, other groups have found evidence of cells that are resistant to damage and are involved in repair and maintenance of tissue. They have proposed that these jun
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
16-Jun-2005


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