title: A new PDAC mouse model originated from iPSCs-converted pancreatic cancer stem cells (CSCcm).
abstract: Pancreatic ductal adenocarcinoma (PDAC) is the most representative form of pancreatic cancers. PDAC solid tumours are constituted of heterogeneous populations of cells including cancer stem cells (CSCs), differentiated cancer cells, desmoplastic stroma and immune cells. The identification and consequent isolation of pancreatic CSCs facilitated the generation of genetically engineered murine models. Nonetheless, the current models may not be representative for the spontaneous tumour occurrence. In the present study, we show the generation of a novel pancreatic iPSC-converted cancer stem cell lines (CSCcm) as a cutting-edge model for the study of PDAC. The CSCcm lines were achieved only by the influence of pancreatic cancer cell lines conditioned medium and were not subjected to any genetic manipulation. The xenografts tumours from CSCcm lines displayed histopathological features of ADM, PanIN and PDAC lesions. Further molecular characterization from RNA-sequencing analysis highlighted primary culture cell lines (1stCSCcm) as potential candidates to represent the pancreatic CSCs and indicated the establishment of the pancreatic cancer molecular pattern in their subsequent progenies 2ndCSCcm and 3rdCSCcm. In addition, preliminary RNA-seq SNPs analysis showed that the distinct CSCcm lines did not harbour single point mutations for the oncogene Kras codon 12 or 13. Therefore, PDAC-CSCcm model may provide new insights about the actual occurrence of the pancreatic cancer leading to develop different approaches to target CSCs and abrogate the progression of this fatidic disease.
authors.affiliation: Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Anna Sanchez
authors.initials: AS
authors.lastname: Calle
authors.affiliation: Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Neha
authors.initials: N
authors.lastname: Nair
authors.affiliation: Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Aung KoKo
authors.initials: AK
authors.lastname: Oo
authors.affiliation: Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Marta
authors.initials: M
authors.lastname: Prieto-Vila
authors.affiliation: Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Koga
authors.affiliation: Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Apriliana Cahya
authors.initials: AC
authors.lastname: Khayrani
authors.affiliation: Department of Chemistry, Faculty of Science, Menoufia University Shebin El-Koam 32511, Egypt.
authors.forename: Maram
authors.initials: M
authors.lastname: Hussein
authors.affiliation: Cancer Biology Graduate Program, School of Medicine, Wayne State University 10 E Warren, Avenue, Suite 2215, Detroit, Michigan 48201, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Hurley
authors.affiliation: Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Arun
authors.initials: A
authors.lastname: Vaidyanath
authors.affiliation: Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Akimasa
authors.initials: A
authors.lastname: Seno
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama 700-8558, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Department of Systems Biology, University of Vic Vic, Barcelona 08500, Spain.
authors.forename: Malu
authors.initials: M
authors.lastname: Calle
authors.affiliation: Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Kasai
authors.affiliation: Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Seno
keywords: CSCcm; Cancer stem cells; PDAC; conditioned medium; iPSCs; pancreatic cancer