Abstract LB-107: Novel biomarkers of non-small cell lung cancer (NSCLC) stem cells
Authors: Feridoun Karimi-Busheri, Victoria Zadorozhny, Daniel L. Shawler, Habib Fakhrai
Journal: Cancer Research (2011)

Abstract Lung cancer is the highest cancer killer and the rate of death in this disease is approximately equal to death caused by colon, breast, prostate, and pancreas combined. However, little is understood about the role of tumor initiating cells in the lung cancer and whether these cells play a major role in initiation, drug resistance, and metastases of this disease. To answer this question we are investigating three approaches to develop therapies that can target lung tumor initiating cells, designated as lungospheres. The first approach consists of screening a library of chemicals to isolate small molecules that can kill or affect the growth of lungospheres. Our second approach is to develop monoclonal antibodies that can target these cells. Finally, we have gene modified lungospheres with a TGF-β antisense vector for potential use as a component of our therapeutic tumor cell vaccine belagenpumatucel-L, which is currently being tested in a randomized, international phase III clinical trial. In the phase II clinical trial the median survival of stages III/IV subjects who entered the trial with stable disease was 44 months and the 5-year survival was also 50 percent. Accordingly, we have launched a program to better understand lung cancer initiating cells and the possible ways they can be used to develop new therapies for lung cancer. Our goal in this study is to investigate the novel and signature markers of NSCLC. Non-small cell lung cancer comprises approximately 80 percent of all lung cancers populations. Here we present data on the isolation and identification of an enriched subpopulation of NSCLC tumor initiating cells derived from the H460 lung cancer cell line. These cells are highly tumorigenic in NOD/SCID mice and as few as 1000 cells developed tumors in mice in 2-week. In contrast the parental tumor cells required 500,000 cells to develop an equivalent tumor in 4-week. Furthermore, tumors developed from the lungospheres exhibit highly congested blood vessels, visibly more vascularized than the tumors developed from the parental cells, demonstrating a more aggressive tumor with a higher metastatic potential. We confirmed the human origin of the tumor performing short tandem repeat technique. We also isolated lungospheres from tumors grown in mice. We have critically examined proposed biomarkers of lung cancer stem cells such as ALDH, EpCAM, CD133/1, CD133/2, CD24, and CD38, using global gene expression, flow cytometric analysis, and quantitative real time PCR. We propose, for the first time, that CD38 in combination with CD24 could potentially be a critical diagnostic factor of lung cancer stem cells. Our results demonstrate that the combination of CD24Low/−/CD38+ is the signature of enriched tumor initiating cells in H460 non-small cell lung cancer cell line. 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 LB-107. doi:10.1158/1538-7445.AM2011-LB-107