start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=1 article-no= start-page=200 end-page=207 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=2020 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Upregulated CCL20 and CCR6 in Cancer Stem Cells Converted from Mouse iPS Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Cancer stem cells (CSCs) as a class of malignant cancer cells play an important role in tumor progression. Previous studies by our group have demonstrated the establishment of the model of CSCs converting mouse iPS cells (miPSCs) into CSCs by treating the miPSCs with a conditioned medium (CM) of Lewis Lung Carcinoma (LLC) cells with or without the nonmutagenic chemical compounds. CSCs converted from miPSCs developed highly malignant adenocarcinoma when subcutaneously transplanted into the nude mice.
Methods: The miPSCs were treated with each compound for 1 week in the presence of a CM of LLC cells. We evaluated the gene expression in the resultant CSCs comparing that in miPSCs by microarray analysis. And the expression of chemokine (C-C motif) ligand 20 (CCL20) and C-C chemokine receptor type 6 (CCR6) in converted cells were evaluated by rt-qPCR. The CCR6 expression in converted cells and primary cells were determined by flow cytometry.
Results: As the result, the expression of CCL20 was found upregulated in the presence of CM supplemented with PD0325901. Then we assessed the expression of CCR6, which was considered to be stimulated by CCL20. Then the expression of CCR6 was also found up-regulated. Interestingly, IL17A expression was also observed only in the CSCs from the primary tumor implying the effect of tumor microenvironment. Moreover, significantly high level of CCR6 was showed in flow cytometric analysis.
Conclusion: These results suggest that a model of CSCs with CCL20-CCR6 autocrine loop was obtained as the result of the conversion of iPSCs. This CSC should be a good model to study targeting CCR6 as a G protein-coupled receptor (GPCR). en-copyright= kn-copyright= en-aut-name=DuJuan en-aut-sei=Du en-aut-mei=Juan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SenoAkimasa en-aut-sei=Seno en-aut-mei=Akimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasadaSaki en-aut-sei=Sasada en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=XuYanning en-aut-sei=Xu en-aut-mei=Yanning kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OoAung Ko Ko en-aut-sei=Oo en-aut-mei=Aung Ko Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HassanGhmkin en-aut-sei=Hassan en-aut-mei=Ghmkin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UenoShunsuke en-aut-sei=Ueno en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AfifySaid M. en-aut-sei=Afify en-aut-mei=Said M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ZahraMaram H en-aut-sei=Zahra en-aut-mei=Maram H kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkadaNobuhiro en-aut-sei=Okada en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ChenLing en-aut-sei=Chen en-aut-mei=Ling kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FuXiaoying en-aut-sei=Fu en-aut-mei=Xiaoying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TokutakaHeizo en-aut-sei=Tokutaka en-aut-mei=Heizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YanTing en-aut-sei=Yan en-aut-mei=Ting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama Universityalth Systems kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics kn-affil= affil-num=12 en-affil=School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine kn-affil= affil-num=13 en-affil=SOM Japan kn-affil= affil-num=14 en-affil=The Hong Kong University of Science and Technology Medical Center, Shenzhen Peking University kn-affil= affil-num=15 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=miPSCs kn-keyword=miPSCs en-keyword=CSCs kn-keyword=CSCs en-keyword=CCR6 kn-keyword=CCR6 en-keyword=CCL20 kn-keyword=CCL20 END