Abstract 4272: Elimination of human lung cancer stem cells through targeting of the SCF-c-kit autocrine signaling loop

Abstract

Abstract Cancer stem cells (CSCs) are thought to be responsible for tumor initiation and tumor regeneration after chemotherapy. Earlier we demonstrated that chemotherapy led to the selection of CSCs and that the high malignancy of lung CSCs was associated with an efficient cytokine network. Here we propose that blocking SCF-c-kit signaling will inhibit CSC proliferation and survival. CSCs were isolated from nonsmal cell lung cancer (NSCLC) cell lines as tumor spheres under CSC-selective conditions, and their stem/progenitor properties were confirmed. A Cellomics ArrayScan HCS Reader was applied to test the cell surface markers, the intracellular protein distribution and cell proliferation. CSCs in contrast to bulk cells expressed high levels of c-kit receptors and produced SCF. Proliferation of CSCs was stimulated by exogenous SCF and was inhibited by antibodies neutralizing SCF and by imatinib (Gleevec), a specific inhibitor of c-kit. Cisplatin treatment eliminated major of bulk cells but not CSCs, whereas imatinib or anti-SCF antibody destroyed CSCs. In combination cisplatin and imatinib or anti-SCF antibody prevented growth of both tumor cell subpopulations. Our results elucidate the important role of SCF-c-kit signaling axis for the self-renewal and proliferation of lung CSCs. Blocking SCF-c-kit signaling by anti-SCF antibody or imatinib in combination with cisplatin could be more efficient in elimination of human tumor cells than each modality used separately. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4272.