Cancer stem cells (CSCs) show drug resistance and could be a source of cancer cells. Although these cells are recently considered more important than ever in cancer studies, the extremely small number of CSCs in actual cancer tissues makes the analysis difficult. Previously, we demonstrated that CSCs could be differentiated from induced pluripotent stem cells (iPSCs) in the presence of cancer cell conditioned media. We have confirmed the conditioned media from various types of cancer cell lines were successful to convert iPSCs into CSCs showing self-renewal property, differentiation potential, and tumorigenicity. To identify their differences between the generated CSCs, gene expression was compared by spherical self-organizing map (sSOM). Comparing with more than 1000 cells including stem cells, induced CSCs, CSCs obtained from cancer tissue or cancer cell line, and cancer cells or cancer tissues, known cancer stem cell markers were found not enough to classify CSCs. In the sSOM analysis, “ideal probe” (IP), which was supposed to characteristically be expressed in each group, was set to nomiate the marker gene. The distance close to the IP depicted some candidate marker genes in each group. The gene expression commonly shared among different types of CSCs was also searched. This IP revealed known cancer related gene Endthelin 1 as a commonly expressed gene. Moreover, when the CSCs were compared with the parental hiPSC and cancer cells, of which conditioned media was used for the conversion, sSOM showed that CSCs were not always differentiated towards their origin, but which genes should be responsible for generating CSCs. These results indicate that the induced CSCs should be the initial state of cancer cells and imply some important role of Endothelin 1 in CSC development.

Citation Format: Akimasa Seno, Tomonari Kasai, Heizo Tokutaka, Masaharu Seno. CSCs induced from iPSCs indicate the trace of cancer cell culture conditioned media [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2005.