Lung cancer is the major cause of death from cancer worldwide. The five-year survival rate for the majority of lung cancer patients is only 16% because their tumors are refractory to chemotherapeutics or quickly become resistant to therapeutic response. Also contributing to morbidity, most lung cancer patients already have advanced, metastatic disease at the time of diagnosis or develop metastases after surgical removal of early-stage primary lung tumors. The cancer stem cell (CSC) hypothesis is an attractive explanation for tumor growth, recurrence after treatment, and metastasis in some cancers, yet the precise role of CSCs in lung tumors has not been established. Since successful cancer therapy requires the elimination or incapacitation of all tumor cells capable of regenerating a tumor, it is crucial to characterize the cells that are able to propagate a tumor in vivo. We refer to these functionally important cancer cells as tumor-propagating cells (TPCs). Importantly, understanding the identity and molecular nature of TPCs will provide new opportunities for early detection, treatment and prevention of metastatic disease, whether or not they fit the CSC model in each type of cancer. My laboratory recently showed that murine lung adenocarcinomas, the most prevalent lung cancer subtype, contain a TPC population. In mice bearing tumors initiated with oncogenic Kras and deletion of p53, the cell surface marker Sca1 identifies cancer cells with stem cell properties. In contrast, TPCs are Sca1-negative in lung tumors that express a mutant EGFR. Thus, the predominant driving oncogenotype is an important determinant in the identification of TPC phenotype in lung cancer. This finding suggests that treatments directed against cancer stem cells should be targeted to subsets of patients grouped according to their oncogenotype. We have recently obtained global gene expression data from the Sca1-sorted populations of murine lung tumor cells, as well as their normal wild-type counterparts, to uncover the molecular pathways responsible for tumor propagation in lung adenocarcinoma. I will also discuss new avenues we have taken to understand the connections between TPCs and metastasis in mouse models as well as translating the importance of our findings in human lung cancer cells and patient samples.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY12-01. doi:10.1158/1538-7445.AM2011-SY12-01