Poster Sessions

CANCER-15

Hobbs Evthokia

E.A. Hobbs, M.C. Hollander, I.R. Linnoila, L.V. Varticovski, K. Harris, C.D. Salcido, B.J. Taylor, D. Schrump, G. Giaccone, P.A. Dennis

Studies to Identify Lung Cancer Stem Cells in a Tobacco Carcinogen-driven Mouse Model

The role of cancer stem cells in solid tumors, specifically tobacco carcinogen-induced lung adenocarcinomas, is controversial and poorly defined. We have begun to isolate and characterize lung cancer stem cells (LCSCs) in 4 cell lines independently derived from lung adenocarcinomas of immunocompetent A/J mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Side population (SP) cells, characterized by the ability to efflux Hoechst 33342 dye, were isolated to potentially enrich for LCSCs. The SP fraction was able to repopulate the original population when cultured in vitro in the presence of serum and in vivo when grown as a subcutaneous tumor. Cell line differences in repopulation were observed. In addition, the SP fraction forms tumors with as few as 10 cells. However, there is no noticeable difference in frequency of tumor formation or volume compared to the parental fraction. Evaluation of other potential biomarkers of LCSCs is also being pursued. An inverse relationship between the bronchioalveolar stem cell maker SCA1 and the SP fraction was observed. The ability of other markers such as CD133 and ALDH1 to enrich LCSC is being investigated. These studies identify the SP fraction as bearing properties of LCSC, but have failed to distinguish the SP fraction from the parental cell lines.