Abstract 248: Stearoyl-CoA desaturase 1 is a key factor for lung cancer stem cell survival and expansion.
Authors: Ciliberto Gennaro , Noto Alessia , De Vitis Claudia , Barzellotti Roberta , Roscilli Giuseppe , Aurisicchio Luigi , Raffa Salvatore , Ricci Alberto , Mariotta Salvatore , Torrisi Maria Rosaria , Giovagnoli Maria Rosaria , Mancini Rita 
Published: August 2014

In recent years studies of cancer development and recurrence have been significantly influenced by the Cancer Stem Cell (CSC) hypothesis. According to this, cancer is sustained by highly-positioned, chemoresistant cells with extensive capacity of self renewal, which are responsible for disease relapse after treatment with debulking agents. Growth of cancer cells as non-adherent spheroids in non differentiating conditions is regarded as a useful methodology to enrich for cells endowed with CSC-like features. We have recently reported that cell cultures derived from Malignant Pleural Effusions (MPE) of patients affected by adenocarcinoma of the lung are able to form spheroids in non-adherent conditions supplemented with selected growth factors, that these spheroids upregulate markers associated with stemness, can be serially propagated in vitro through several passages and, finally, give rise efficiently to tumors, which reproduce the same histopathological features of the original human tumor when implanted in immunodeficient mice. By expression profiling we also identified a set of genes whose expression is significantly upregulated in lung tumor spheroids vs adherent cultures. One of the most strongly upregulated gene was Stearoyl-CoA desaturase (SCD1), the main enzyme responsible for the conversion of saturated into monounsaturated fatty acids. In the present study we show both by RNA interference or through the use of a small molecule inhibitor that SCD1 is required for lung cancer spheroids propagation both in stable cell lines and in primary tumor cultures. SCD1 inhibition causes a dramatic impairment of survival of cells which express ALDH and other markers of stemness in vitro. Morphological examination and image analysis of the tumor spheroids formed in the presence of SCD1 inhibitors showed a different pattern of growth characterized by irregular cell aggregates. Electron microscopy revealed that the treated spheroids displayed several features of cellular damage and immunofluorescence analysis on optical serial sections showed apoptotic cells positive for the M30 marker, most of them positive also for the stemness marker ALDH, thus suggesting that the SCD1 inhibitor is selectively killing cells with stem like properties. Furthermore, SCD1-inhibited lung cancer spheroids were strongly impaired in their in vivo tumorigenicity. These results suggest that SCD1 is a critical target in lung cancer tumor initiating cells.

Citation Format: Gennaro Ciliberto, Alessia Noto, Claudia De Vitis, Roberta Barzellotti, Giuseppe Roscilli, Luigi Aurisicchio, Salvatore Raffa, Alberto Ricci, Salvatore Mariotta, Maria Rosaria Torrisi, Maria Rosaria Giovagnoli, Rita Mancini. Stearoyl-CoA desaturase 1 is a key factor for lung cancer stem cell survival and expansion. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 248. doi:10.1158/1538-7445.AM2013-248