Cancer stem cells have been identified in many tumors, including lung cancer. However, there is no unified method to identify and isolate these cells from different tumors. Side population (SP) cells, identified by exclusion of Hoechst dye, has led to identification of cells with stem cell characteristics from normal tissues, as well as from several tumors and established cell lines. Small cell carcinoma of the lung (SCLC) is a highly aggressive tumor that is frequently metastatic at presentation. These tumors rapidly become resistant to chemotherapy and radiation with overall survival of less than 10% in 5 years. These features suggest that SCLC may be enriched in cancer stem cells. To identify cancer stem cell population from SCLC, we characterized SP fraction cells from several established human cell lines. Sorted SP cells had higher proliferative capacity than did Non-SP cells, and rapidly reconstituted the original population in vitro. In contrast to other reports, as few as 50 cells SP fraction sorted cells from NCI-H146 and NCI-H526 SCLC cell lines were sufficient to reconstitute tumors within 30 days, a 100-fold enrichment in tumor-initiating cells as compared to cells from Non-SP fraction. SP cells displayed lower levels of cell surface markers associated with differentiation, such as CD56 and CD90 and overexpressed many genes activate in normal stem cells, including FGF1, IGF1, ABCG2, and many other genes associated with stem cell regulatory pathways and angiogenesis, such as Notch, Shh and VEGF. Expression of these and other genes associated with normal and malignant stem cells was validated by qPCR. Thus, SP cells from SCLC are highly enriched in cancer stem cells. Further studies of this cell population could provide clues for development of cancer stem cell-targeted therapies for this rapidly fatal lung cancer.
Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 176.
100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO