A new PDAC mouse model originated from iPSCs-converted pancreatic cancer stem cells (CSCcm)

Anna Sanchez Calle, Neha Nair, Aung Ko Ko Oo, Marta Prieto-Vila, Megumi Koga, Apriliana Cahya Khayrani, Hussein Maram, Laura Hurley, Arun Vaidyanath, Akimasa Seno, Yoshiaki Iwasaki, Malu Calle, Tomonari Kasai, Masaharu Seno

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 (1st CSCcm) as potential candidates to represent the pancreatic CSCs and indicated the establishment of the pancreatic cancer molecular pattern in their subsequent progenies 2nd CSCcm and 3rd CSCcm. 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.

Original languageEnglish
Pages (from-to)2799-2815
Number of pages17
JournalAmerican Journal of Cancer Research
Volume6
Issue number12
Publication statusPublished - 2016

Keywords

  • Cancer stem cells
  • Conditioned medium
  • CSCcm
  • IPSCs
  • Pancreatic cancer
  • PDAC

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Calle, A. S., Nair, N., Oo, A. K. K., Prieto-Vila, M., Koga, M., Khayrani, A. C., Maram, H., Hurley, L., Vaidyanath, A., Seno, A., Iwasaki, Y., Calle, M., Kasai, T., & Seno, M. (2016). A new PDAC mouse model originated from iPSCs-converted pancreatic cancer stem cells (CSCcm). American Journal of Cancer Research, 6(12), 2799-2815.