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Dysregulation of Iron Metabolism in Cholangiocarcinoma Stem-like Cells

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

  • Chiara Raggi
  • Elena Gammella
  • Margherita Correnti
  • Paolo Buratti
  • Elisa Forti
  • Andersen, Jesper Bøje
  • Gianfranco Alpini
  • Shannon Glaser
  • Domenico Alvaro
  • Pietro Invernizzi
  • Gaetano Cairo
  • Stefania Recalcati

Cholangiocarcinoma (CCA) is a devastating liver tumour arising from malignant transformation of bile duct epithelial cells. Cancer stem cells (CSC) are a subset of tumour cells endowed with stem-like properties, which play a role in tumour initiation, recurrence and metastasis. In appropriate conditions, CSC form 3D spheres (SPH), which retain stem-like tumour-initiating features. Here, we found different expression of iron proteins indicating increased iron content, oxidative stress and higher expression of CSC markers in CCA-SPH compared to tumour cells growing as monolayers. Exposure to the iron chelator desferrioxamine decreased SPH forming efficiency and the expression of CSC markers and stem-like genes, whereas iron had an opposite effect. Microarray profiles in CCA samples (n = 104) showed decreased H ferritin, hepcidin and ferroportin expression in tumours respect to surrounding liver, whereas transferrin receptor was up-regulated. Moreover, we found a trend toward poorer outcome in CCA patients with elevated expression of ferritin and hepcidin, two major proteins of iron metabolism. These findings, which represent the first evidence of a role for iron in the stem cell compartment as a novel metabolic factor involved in CCA growth, may have implications for a better therapeutic approach.

OriginalsprogEngelsk
Artikelnummer17667
TidsskriftScientific Reports
Vol/bind7
Udgave nummer1
Antal sider12
ISSN2045-2322
DOI
StatusUdgivet - 1 dec. 2017

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