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  • Steiner, S. (author)

De novo expression of gastrokines in pancreatic precursor lesions impede the development of pancreatic cancer

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-01-26
  • Springer Science and Business Media LLC,2022

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/313881
  • https://gup.ub.gu.se/publication/313881URI
  • https://doi.org/10.1038/s41388-022-02182-4DOI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Molecular events occurring in stepwise progression from pre-malignant lesions (pancreatic intraepithelial neoplasia; PanIN) to the development of pancreatic ductal adenocarcinoma (PDAC) are poorly understood. Thus, characterization of early PanIN lesions may reveal markers that can help in diagnosing PDAC at an early stage and allow understanding the pathology of the disease. We performed the molecular and histological assessment of patient-derived PanINs, tumor tissues and pancreas from mouse models with PDAC (KC mice that harbor K-RAS mutation in pancreatic tissue), where we noted marked upregulation of gastrokine (GKN) proteins. To further understand the role of gastrokine proteins in PDAC development, GKN-deficient KC mice were developed by intercrossing gastrokine-deficient mice with KC mice. Panc-02 (pancreatic cancer cells of mouse origin) were genetically modified to express GKN1 for further in vitro and in vivo analysis. Our results show that gastrokine proteins were absent in healthy pancreas and invasive cancer, while its expression was prominent in low-grade PanINs. We could detect these proteins in pancreatic juice and serum of KC mice. Furthermore, accelerated PanIN and tumor development were noted in gastrokine deficient KC mice. Loss of gastrokine 1 protein delayed apoptosis during carcinogenesis leading to the development of desmoplastic stroma while loss of gastrokine 2 increased the proliferation rate in precursor lesions. In summary, we identified gastrokine proteins in early pancreatic precursor lesions, where gastrokine proteins delay pancreatic carcinogenesis.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Seleznik, G. M. (author)
  • Reding, T. (author)
  • Stopic, M. (author)
  • Lenggenhager, D. (author)
  • ten Buren, E. (author)
  • Eshmuminov, D. (author)
  • Endhardt, K. (author)
  • Hagedorn, C. (author)
  • Heidenblut, A. M. (author)
  • Bratus-Neuenschwander, A. (author)
  • Grossmann, J. (author)
  • Trachsel, C. (author)
  • Jabbar, Karolina S.Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology(Swepub:gu)xsjobk (author)
  • Hahn, S. A. (author)
  • Berg, J. (author)
  • Graf, R. (author)
  • Gupta, A. (author)
  • Göteborgs universitetInstitutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi (creator_code:org_t)

Related titles

  • In:Oncogene: Springer Science and Business Media LLC41, s. 1507-15170950-92321476-5594

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