Dysregulation of Iron Metabolism in Cholangiocarcinoma Stem-like Cells

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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Article number17667
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

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Cholangiocarcinoma
Stem Cells
Iron
Neoplastic Stem Cells
Hepcidins
Neoplasms
Apoferritins
Transferrin Receptors
Deferoxamine
Liver
Ferritins
Chelating Agents
Bile Ducts
Proteins
Oxidative Stress
Epithelial Cells
Neoplasm Metastasis
Recurrence
Growth
Genes

ASJC Scopus subject areas

  • General

Cite this

Raggi, C., Gammella, E., Correnti, M., Buratti, P., Forti, E., Andersen, J. B., ... Recalcati, S. (2017). Dysregulation of Iron Metabolism in Cholangiocarcinoma Stem-like Cells. Scientific Reports, 7(1), [17667]. https://doi.org/10.1038/s41598-017-17804-1

Dysregulation of Iron Metabolism in Cholangiocarcinoma Stem-like Cells. / Raggi, Chiara; Gammella, Elena; Correnti, Margherita; Buratti, Paolo; Forti, Elisa; Andersen, Jesper B.; Alpini, Gianfranco; Glaser, Shannon; Alvaro, Domenico; Invernizzi, Pietro; Cairo, Gaetano; Recalcati, Stefania.

In: Scientific Reports, Vol. 7, No. 1, 17667, 01.12.2017.

Research output: Contribution to journalArticle

Raggi, C, Gammella, E, Correnti, M, Buratti, P, Forti, E, Andersen, JB, Alpini, G, Glaser, S, Alvaro, D, Invernizzi, P, Cairo, G & Recalcati, S 2017, 'Dysregulation of Iron Metabolism in Cholangiocarcinoma Stem-like Cells', Scientific Reports, vol. 7, no. 1, 17667. https://doi.org/10.1038/s41598-017-17804-1
Raggi C, Gammella E, Correnti M, Buratti P, Forti E, Andersen JB et al. Dysregulation of Iron Metabolism in Cholangiocarcinoma Stem-like Cells. Scientific Reports. 2017 Dec 1;7(1). 17667. https://doi.org/10.1038/s41598-017-17804-1
Raggi, Chiara ; Gammella, Elena ; Correnti, Margherita ; Buratti, Paolo ; Forti, Elisa ; Andersen, Jesper B. ; Alpini, Gianfranco ; Glaser, Shannon ; Alvaro, Domenico ; Invernizzi, Pietro ; Cairo, Gaetano ; Recalcati, Stefania. / Dysregulation of Iron Metabolism in Cholangiocarcinoma Stem-like Cells. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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