Title of Research:
13_S01-01-3

Development of novel method to evaluate the indicibility of cancer
stem cells from iPS cells in chemical compounds
Principal Investigator:
Masaharu Seno, Graduate School of Natural Science and Technology Okayama UniversityCollaborators:
Tomonari Kasai, Graduate School of Natural Science and Technology Okayama University
Shuichi Furuya, Okayama University Research Administration office
Akifumi Mizutani, Graduate School of Natural Science and Technology Okayama University
Jyunko Masuda, Graduate School of Natural Science and Technology Okayama University
Akimasa Seno, Graduate School of Natural Science and Technology Okayama University
Summary of Research:
Cancer stem cells are typically characterized by continuous proliferation self-renewal as well as
by differentiation potential, while stem cells are considered to differentiate into tissue specificphenotype of mature cells under the influence of microenvironment. Cancer stem cells can betraced back to the stem cells under specific influences of microenvironment, so called ‘cancerous
niche’, which induces malignant tumors. We have very recently demonstrated the induction ofcancer stem cells from mouse iPS cells culturing in the conditioned medium derived from cancercells, although the details of the mechanisms of differentiation is not very well known as of yet.
In this study, we aim for the development of novel method to evaluate the risk of chemicalcompounds for the potential to induce cancer stem cells from iPS cells in vitro in a short period.
Briefly, mouse iPS cells are suspended in the conditioned medium. The cells are further
replenished with the growth medium with the compounds to be assessed.
We are currently observing the fluorescence intensity of GFP, which corresponds to the active
Nanog promoter, and establishing the method for detecting the risk of compounds which accrete
CSC conversion. The modification for usable method and high sensibility is under way. We areinvestigating the epigenetic analysis by RRBS (Reduced Representation Bisulfite Sequencing)and DMR (Differentially methylated regions) analysis.
Timeline:
March 2012-February 2016
Publications:1.
Prieto-Vila M, Yan T, Calle AS, Nair N, Hurley L, Kasai T, Kakuta H, Masuda J, Murakami
H, Mizutani A, Seno M. iPSC-derived cancer stem cells provide a model of tumor vasculature. AmJ Cancer Res. 2016 Sep 1;6(9):1906-1921.
2.
Seno A, Kasai T, Ikeda M, Vaidyanath A, Masuda J, Mizutani A, Murakami H, Ishikawa T,Seno M. Characterization of Gene Expression Patterns among Artificially Developed Cancer StemCells Using Spherical Self-Organizing Map. Cancer Inform. 2016 Aug 16;15:163-178.
3.
Calle AS, Nair N, Oo AK, Prieto-Vila M, Koga M, Khayrani AC, Hussein M, Hurley L,
Vaidyanath A, Seno A, Iwasaki Y, Calle M, Kasai T, Seno M. A new PDAC mouse model originatedfrom iPSCs-converted pancreatic cancer stem cells (CSCcm). Am J Cancer Res. 2016 Dec
1;6(12):2799-2815.
Conferences:
1.
Takayuki Kudoh, Saki Sasada, Junko Masuda, Masashi Ikeda, Takuma Matsumoto, Anna
Sanchez Calle, Neha Nair, Mami Asakura, Tomonari Kasai, Masaharu Seno. Exploration of Target
Molecules and Related Pathways Affecting the Conversion of iPSCs into Cancer Stem Cells by
Chemical Compounds. IIBMP 2016, (Sep 29-Oct 1,Tokyo)
2.
Matumoto T, Sasada S, Ikeda M, Calle AS, Kasai T, Seno M. Elucidation of inducible
mechanism of cancer stem cells with chemical compounds. MBSJ 2016, 39 th (Nov 30-Dec 2,Yokohama)