title: Susceptibility of pancreatic cancer stem cells to reprogramming.
abstract: Previous reports have indicated that reprogramming technologies may be useful for altering the malignant phenotype of cancer cells. Although somatic stem cells in normal tissues are more sensitive to reprogramming induction than differentiated cells, it remains to be elucidated whether any specific subpopulations are sensitive to reprogramming in heterogeneous tumor tissues. Here we examined the susceptibility of pancreatic cancer stem cells (CSC) and non-CSC to reprogramming. To characterize CSC populations, we focused on c-Met signaling, which has been identified as a marker of CSC in mouse experiments in vivo. Cells that expressed high levels of c-Met showed higher CSC properties, such as tumor-initiating capacity, and resistance to gemcitabine. Real-time reverse transcription-polymerase chain reaction in cells expressing high levels of c-Met revealed endogenous expression of reprogramming factors, such as OCT3/4, SOX2, KLF4 and cMYC. Introduction of these four factors resulted in higher alkaline phosphatase staining in cells with high c-Met expression than in controls. Therefore, the study results demonstrate that cellular reprogramming may be useful for extensive epigenetic modification of malignant features of pancreatic CSC.
authors: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.|Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors: Kozo
authors: K
authors: Noguchi
authors: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors: Hidetoshi
authors: H
authors: Eguchi
authors: Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors: Masamitsu
authors: M
authors: Konno
authors: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors: Koichi
authors: K
authors: Kawamoto
authors: Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors: Naohiro
authors: N
authors: Nishida
authors: Department of Cancer Profiling Discovery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors: Jun
authors: J
authors: Koseki
authors: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors: Hiroshi
authors: H
authors: Wada
authors: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors: Shigeru
authors: S
authors: Marubashi
authors: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors: Hiroaki
authors: H
authors: Nagano
authors: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors: Yuichiro
authors: Y
authors: Doki
authors: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors: Masaki
authors: M
authors: Mori
authors: Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan.|Department of Cancer Profiling Discovery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors: Hideshi
authors: H
authors: Ishii
mesh_terms: D045744:Cell Line, Tumor; D065150:Cellular Reprogramming / Q000502:physiology*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000502:physiology*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000503:physiopathology*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; D016271:Proto-Oncogene Proteins c-myc; D055748:SOXB1 Transcription Factors; D019859:Proto-Oncogene Proteins c-met
keywords: Cancer stem cell; cancer therapy; induced pluripotent stem cell; pancreatic cancer; reprogramming