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Title: Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells
Authors: Rodrigues, Carlos F. D. 
Serrano, Eurico 
Patrício, Maria I.
Val, Mariana
Albuquerque, Patrícia
Fonseca, João 
Gomes, Célia M. F. 
Abrunhosa, Antero 
Paiva, Artur 
Carvalho, Lina 
Botelho, Maria F. 
Almeida, Luís 
Carreira, Isabel M. 
Alpoim, Maria Carmen 
Issue Date: 1-Aug-2018
Publisher: Springer Nature
Serial title, monograph or event: Scientific Reports
Volume: 8
Issue: 1
Abstract: Cancer stem cells (CSCs) are a small population of resistant cells inhabiting the tumors. Although comprising only nearly 3% of the tumor mass, these cells were demonstrated to orchestrate tumorigenesis and differentiation, underlie tumors' heterogeneity and mediate therapy resistance and tumor relapse. Here we show that CSCs may be formed by dedifferentiation of terminally differentiated tumor cells under stress conditions. Using a elegant co-culture cellular system, we were able to prove that nutrients and oxygen deprivation activated non-malignant stromal fibroblasts, which in turn established with tumor cells a paracrine loop mediated by Interleukine-6 (IL-6), Activin-A and Granulocyte colony-stimulating factor (G-CSF), that drove subsequent tumor formation and cellular dedifferentiation. However, by scavenging these cytokines from the media and/or blocking exosomes' mediated communication it was possible to abrogate dedifferentiation thus turning these mechanisms into potential therapeutic targets against cancer progression.
ISSN: 2045-2322
DOI: 10.1038/s41598-018-29947-w
Rights: openAccess
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais
FFUC- Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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