Abstract 501: Characterization of lung cancer stem/initiating cells from non-small-cell lung cancer patients

Abstract

Abstract Cancer stem cells (CSCs) have been proposed to be responsible for chemoresistant, tumor recurrent, and metastasis. To culture and characterize the CSCs become urgent and may be helpful to develop novel diagnostic and therapeutic strategies. Accumulated evidences indicated the importance of CSCs in tumor formation and successfully isolated the CSCs from patients or cell lines with different cancer types; however, this has not been well explored in lung cancer. Not alike previous isolation through specific markers and quiescent condition, we cultured the lung cancer stem/initiating cells from patient with lung adenocarcinoma and the CSCs formed tumor sphere as fed by the surrounding stroma cells. These lung cancer stem/initiating cells were characterized with highly expressed levels of the stemness makers, nanog, oct4, sox2, and klf4 (53.3-, 37.7-, 13.0, and 4.4-folds changes) as comparing to the feeder cells, also, showed relative higher percentages of side population (27.4%), ALDH activity (14%), higher tumorigenesity compared to other lung cancer cell lines including adenocarcinoma (A549, H522, H23, Hop62, and EKVX), large cell carcinoma (Hop92), squamous cell carcinoma (H226), and bronchi alveolar carcinoma (H322M). These lung CSCs also showed higher drug resistance capacity represented by IC50 to chemotherapy drugs including docetaxel, cisplatin, vinorelbine distrate, and etoposide (13.0-, 1.55, 27.2- and 103.3-folds increased). Furthermore, we found that as less as 100 cells could generate adenocarcinoma formation both in orthotropic or subcutaneous models in severe combined immunodeficient (NOD/SCID) mice. Interestingly, the lung CSCs could spontaneous differentiate into epithelial types of cancer cells as removing the feeder cells in vitro or different phenotypes of adenocarcinoma cells in vivo. Transcriptomic analysis indicated that the Wnt, Notch, TGF-β and HGF signaling pathways are highly expressed in the lung CSCs and quickly down-regulated as removing the feeder cells. The gene expression profiles also provide the novel markers for selection CSCs from lung cancer cell lines and lung cancer patients. To sum up, we have cultured the cancer stem/initiating cells from lung cancer patient with the feeder cells, which providing the tumor microenvironment to maintain the stemness of the cancer stem cells. This model should be helpful not only for isolating and cultured the lung CSCs from patients, but also in developing the anti-cancer strategy targeting on lung CSCs. 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 501. doi:10.1158/1538-7445.AM2011-501