CN18-01

It has been demonstrated that some types of tumors (e.g. breast, brain, and lymphoid tumors) harbor a cancer stem cell (CSC) population that is required to maintain malignancy and which may harbor resistance to current therapeutic strategies. However, it is unknown whether lung cancers similarly harbor a cancer stem cell population. The identification and characterization of Bronchioalveolar Stem Cells (BASCs), putative resident stem cells of the distal lung, has suggested that these cells are important in normal lung homeostasis, lung tumor initiation and cancer progression. In mouse models of lung adenocarcinomas, BASCs undergo expansion after oncogene activation and/or tumor suppressor loss, and BASC-like cells persist within the developed tumors. We hypothesize that BASC-like cells within these lesions play a critical role in tumor maintenance. To address this question, we have developed an assay to test for lung CSCs. Orthotopic transplantations of primary murine lung adenocarcinoma cells via intratracheal injections into nude mice yield secondary tumors that recapitulate the features of the primary lung tumors. Transplantation of specific cell subsets from primary tumors into secondary hosts is currently being performed for comparison of their capacity for tumorigenesis. Our current data suggest that the BASC-like cells and the remaining tumor cells, once present within an established tumor, are equally sufficient to function as lung cancer stem cells. Further work will be needed to identify markers that will be useful for isolating a lung cancer stem cell population.

Sixth AACR International Conference on Frontiers in Cancer Prevention Research-- Dec 5-8, 2007; Philadelphia, PA