We previously discovered a population of stem cells named BronchioAlveolar Stem Cells (BASCs) in the mouse lung.  BASCs reside in the bronchioalveolar junction and appear to be important for maintaining bronchiolar and alveolar cells during normal lung homeostasis. Using a mouse model that mimics the most common form of lung cancer in humans, we determined that BASCs may be the cells-of-origin of lung adenocarcinoma. Recent work in other solid tumors indicates that stem cells may also be important in the continued growth of tumors; in breast, colon, and brain cancers, only a small fraction of the cells are required for tumor growth in transplantation assays. These rare cancer cells have been named “cancer stem cells,” and it is hypothesized that they are resistant to chemotherapeutic agents. In order to cure cancer, it may be crucial to develop treatments that specifically eliminate cancer stem cells. However, it is not known if cancer stem cells play a role in lung cancers.

Bronchioalveolar carcinoma (BAC) is a subtype of lung cancer that is usually resistant to traditional chemotherapeutic strategies, raising the possibility that BACs contain a population of cancer stem cells. BAC arises in the terminal bronchioalveolar regions and usually exhibits features of bronchiolar and/or alveolar cells.  Given that human BAC occurs in same anatomical location where we identified BASCs in murine lung, there are likely to be similarities between BASC and BAC biology. Therefore, our prior discovery of BASCs makes our group uniquely positioned to develop new strategies to study BAC. 

]We hypothesize that bronchioalveolar carcinomas (BAC) are maintained by a cancer stem cell population. The Specific Aims of our research are (1) To identify BAC stem cells using murine transplantation assays and (2) To use stem cell culture methods to identify chemicals that inhibit BAC stem cells.  First, we will compare the ability of isolated human BAC cell populations to propagate lung cancer in immunocompromised mice. We will use currently defined BASC markers and markers of cancer stem cells from other tissues to identify a cancer stem cell population in BAC. In parallel studies, we will use our BASC culture system to propagate BAC cells and perform a screen to identify small molecules that inhibit stem cell properties of BAC cells.

Understanding how to distinguish lung cancer stem cells from other tumor cells will highlight new ways to study and treat BAC. If drugs can be developed to inhibit the growth of the cancer stem cells we identify, they may be the most promising form of therapy for BAC patients. The unique features of BAC stem cells may also be useful as indicators of tumor severity or for imaging tumor growth in patients.